Bio

Clinical Focus


  • Hodgkin's Disease
  • Medical Oncology
  • Mycosis Fungoides
  • Non-Hodgkin's Lymphoma
  • Lymphoma
  • Burkitt's Lymphoma
  • Waldenstrom's Macroglobulinemia
  • Plasmacytoma
  • Oncology (Cancer)
  • Burkitt's Lymphoma - Medical Oncology
  • Cancer > Lymphoma
  • Burkitt's Lymphoma - Hematology
  • Investigational Therapeutics
  • Leptommeningeal Disease

Academic Appointments


Administrative Appointments


  • Lymphoma DMG leader, Stanford Cancer Institute (2010 - Present)

Professional Education


  • Internship:Santa Clara Valley Medical Center (1987) CA
  • Fellowship:Stanford University School of Medicine (1996) CA
  • Residency:Stanford University School of Medicine (1990) CA
  • Board Certification: Medical Oncology, American Board of Internal Medicine (1995)
  • Medical Education:Bombay University (1982) India

Community and International Work


  • Stanford Biomarkers Consortium

    Topic

    Biomarkers in lymphomas

    Partnering Organization(s)

    Community Physicians

    Populations Served

    greater bay area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Research & Scholarship

Current Research and Scholarly Interests


Clinical investigation in Hodgkin's disease, non-Hodgkin's Lymphomas and cutaneous lymphomas. Experimental therapeutics with novel chemotherapy and biologically targeted therapies.

The research program is highly collaborative with radiation oncology, industry, pathology and dermatology.

Clinical Trials


  • Pilot Study of Brentuximab Vedotin (SGN-35) in Patients With MF With Variable CD30 Expression Level Recruiting

    The purpose of this study is to learn the effects of an investigational medication, SGN 35, on patients with cutaneous T cell lymphoma (CTCL), specifically mycosis fungoides (MF) and Sezary syndrome (SS). Despite a wide range of therapeutic options, the treatments are associated with short response duration, thus this condition is largely incurable. This investigational drug may offer less toxicity than standard treatments and have better tumor specific targeting. The primary objective is to explore the biologic activity of brentuximab vedotin (SGN-35) in patients with mycosis fungoides (MF) and Sézary syndrome (SS), the most common types of cutaneous T-cell lymphoma (CTCL), where expression of CD30 is variable. SGN-35 has significant biologic activity in Hodgkin's disease (HD) where only a small numbers of CD30 positive tumor cells are present, as well as in lymphomas with large numbers of CD30-expressing tumor cells such as systemic anaplastic large cell lymphoma (sALCL). This phase II exploratory study will evaluate the clinical response of brentuximab vedotin (SGN-35) in MF and SS where tumor cells express variable levels of CD30 target molecule. The grouping by CD30 expression levels (low, intermediate, high) is for accrual purposes only to ensure a wide range of CD30 expression. Given the exploratory nature of this study, it will be open-label, single-arm, and non-randomized trial. One centers will be involved to complete the accrual, a total of 24 patients with MF and SS. Enrollment will be based on CD30 expression levels by tissue immunohistochemistry (IHC), defined as low, intermediate or high expressers. The investigators will target 8 patients in each group for total of 24 patients. Of these 8 patients per group, up to 3 may be patients with SS. Each patient regardless of CD30 expression level will receive 1.8 mg/kg of SGN-35 IV every 21 days, up to 8 cycles of therapy. Patients with CR may receive 2 additional cycles. Patients who have PR may receive up to a maximum of 16 doses IF they are continuing to improve after 8 cycles. Patients who relapse within 6 months after CR maybe eligible for retreatment.

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  • Safety and Tolerability Study of SNS-314 for Advanced Solid Tumors Not Recruiting

    This is a study to assess the safety and tolerability of SNS-314 in advanced solid tumors in humans.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • A Study for Patients With Relapsed Cutaneous T-Cell Lymphoma Not Recruiting

    The purpose of the study is to determine the efficacy and safety of enzastaurin in patients with CTCL who failed prior therapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Safety Study of ABT-263 in Combination With Rituximab in Lymphoid Cancers Not Recruiting

    This is a Phase 1 study evaluating the safety of ABT-263 administered in combination with rituximab in subjects with CD20-positive lymphoproliferative disorders.

    Stanford is currently not accepting patients for this trial. For more information, please contact Euodia Jonathan, (650) 725 - 6432.

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  • Study of Oral LBH589 in Adult Patients With Refractory/Resistant Cutaneous T-Cell Lymphoma Not Recruiting

    This study will evaluate the safety and efficacy of LBH589B in adult patients with refractory/resistant Cutaneous T-Cell Lymphoma and prior HDAC inhibitor therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • A Phase II Trial of Ofatumumab in Subjects With Waldenstrom's Macroglobulinemia Not Recruiting

    Given the tolerability and efficacy of ofatumumab in follicular lymphoma and Chronic Lymphocytic Leukemia, and the need to improve therapy for patients with WM utilizing a non-myelosuppressive agent this phase II trial of ofatumumab is being initiated in patients with Waldenstrom's Macroglobulinemia (WM).

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Study of SGN-40 in Patients With Relapsed Diffuse Large B-Cell Lymphoma Not Recruiting

    This is a Phase II, open-label, multidose trial of SGN-40 designed to estimate objective response rate and assess toxicity in patients with relapsed DLBCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ranjana Advani, (650) 724 - 8372.

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  • Lenalidomide in Treating Patients With Relapsed Mycosis Fungoides/Sezary Syndrome Not Recruiting

    RATIONALE: Lenalidomide may stop the growth of mycosis fungoides/Sezary syndrome by blocking blood flow to the cancer. PURPOSE: This phase II trial is studying how well lenalidomide works in treating patients with relapsed mycosis fungoides/Sezary syndrome.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Photopheresis as an Interventional Therapy for the Treatment of CTCL (Cutaneous T-Cell Lymphoma, Mycosis Fungoides) Stage 1A, 1B, 2A Not Recruiting

    The study objective is to demonstrate that the UVADEX® Sterile Solution formulation of methoxsalen used in conjunction with the UVAR XTS Photopheresis System can have a clinical effect on the skin manifestations of CTCL (mycosis fungoides) in early stage disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • A Study Of PF-05082566 As A Single Agent And In Combination With Rituximab Recruiting

    A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).

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  • Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma Not Recruiting

    Patients meeting specific inclusion and exclusion criteria will be enrolled in two stages, 19 patients in Stage 1 and 36 patients in Stage 2. Stage 2 will enroll if 4 or more patients exhibit a response at Week 8 or later in the study. All enrolled patients will be treated with Fostamatinib Disodium until disease progression. Efficacy will be assessed by tumor measurements using CT and PET (when indicated) scans and physical exam at baseline, and scans and physical exam of all disease-involved areas every 8 weeks until progression. Safety will be assessed by periodic physical exams, clinical laboratory studies, and adverse events. All patients will have a follow-up visit 30 days following last study drug treatment. Blood samples for PK assessment will be obtained from all patients enrolled in Stage 1 at protocol defined intervals.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • A Study of Brentuximab Vedotin in Relapsed or Refractory Non-Hodgkin Lymphoma Recruiting

    This is an open-label, multicenter, phase 2 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in patients with CD30-positive non-Hodgkin lymphoma (NHL) (Part A). The study will also evaluate the safety and efficacy of brentuximab vedotin in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Part B) as well as further evaluate correlation of CD30 expression and response in DLBCL (Part C).

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  • Cardiac Safety Study of Brentuximab Vedotin (SGN-35) Not Recruiting

    The purpose of this study is to evaluate cardiac safety of brentuximab vedotin (SGN-35) in patients with CD30-positive cancers. The study will assess electrical activity of the heart before and after brentuximab vedotin administration. Patients who have stable or improving disease may receive up to 1 year of brentuximab vedotin treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Euodia Jonathan, (650) 725 - 6432.

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  • FLT-PET/CT vs FDG-PET/CT for Therapy Monitoring of Diffuse Large B-cell Lymphoma Recruiting

    Patients will undergo conventional staging methods (CSM), including PDG-PET/CT, for their disease within 4 weeks prior to planned initiation of R-CHOP given for 6 cycles every 3 weeks. These patients will then have FLT-PET/CT and FDG-PET/CT scans performed 18-24 days after the second cycle of R-CHOP. After completion of six cycles of chemotherapy, CSM will be repeated, including FDG-PET/CT but only if the post cycle 2 FDG-PET/CT was positive to assess response and determine the appropriate patient management.

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  • A Study to Evaluate the Efficacy and Safety of Ibrutinib, in Patients With Mantle Cell Lymphoma Who Progress After Bortezomib Therapy Recruiting

    The purpose of this study is to evaluate the efficacy and safety of ibrutinib in patients with mantle cell lymphoma who received at least 1 prior rituximab-containing chemotherapy regimen and who progressed after bortezomib therapy.

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  • Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma Not Recruiting

    This phase II trial studies how well combination chemotherapy and pralatrexate works in treating patients with non-Hodgkin lymphoma (NHL). Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • S0016 Combination Chemotherapy With Monoclonal Antibody Therapy in Treating Patients With Newly Diagnosed Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver radioactive tumor-killing substances to them without harming normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy regimen is more effective in treating non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies given together with combination chemotherapy to see how well they work in treating patients with newly-diagnosed non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lauren Pernicka, (650) 721 - 6977.

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  • Safety and Efficacy of PCI-32765 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma (MCL) Not Recruiting

    The purpose of this study is to: 1. Evaluate the efficacy of PCI-32765 in relapsed/refractory subjects with MCL. 2. The secondary objective is to evaluate the safety of a fixed daily dosing regimen of PCI-32765 capsules in this population.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma Recruiting

    RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bendamustine hydrochloride and rituximab together alone is more effective than giving bendamustine hydrochloride and rituximab together with bortezomib or lenalidomide in treating follicular lymphoma. PURPOSE: This randomized phase II trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage II, stage III, or stage IV follicular lymphoma.

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  • Study of Pralatrexate & Gemcitabine With B12 & Folic Acid to Treat Relapsed/Refractory Lymphoproliferative Malignancies Not Recruiting

    This study is for patients with lymphoproliferative malignancies that have progressed after receiving a previous treatment (relapsed) or are no longer responding to treatment (refractory). To be in this study, patients must have certain types of Hodgkin's lymphoma (HL), peripheral T-cell lymphoma (PTCL), or B-cell lymphoma, including Waldenstrom's macroglobulinemia. This study is being done to find doses of the combination of pralatrexate and gemcitabine with vitamin B12 and folic acid that can be safely given to patients with these types of lymphoma and explore the effectiveness of the treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Safety Study to Evaluate Monoclonal Antibody KW-0761 in Subjects With Peripheral T-cell Lymphoma Not Recruiting

    This study will determine the maximum dose of KW-0761 administered intravenously that can be given safely in subjects with previously treated peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma(CTCL)and will see if it is effective in treating the disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Katie Turner, (650) 725 - 1202.

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  • S0816 Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. G-CSF may help lessen the side effects in patients receiving chemotherapy. Imaging procedures, such as fludeoxyglucose F 18-PET/CT imaging, may help doctors predict how patients will respond to treatment. PURPOSE: This phase II trial is studying fludeoxyglucose F 18-PET/CT imaging to see how well it works in assessing response to combination chemotherapy and allow doctors to plan better additional further treatment in treating patients with stage III or stage IV Hodgkin lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Pitsiouni, (650) 721 - 6977.

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  • Low-dose (12 Gy) TSEBT+Vorinostat Versus Low-dose TSEBT Monotherapy in Mycosis Fungoides Not Recruiting

    The purpose of this study is to determine if vorinostat combined with low-dose total skin electron beam therapy (TSEBT) offers superior clinical benefit (efficacy & safety) over low-dose TSEBT alone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, 650-421-6370.

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  • A Study of ONTAK and CHOP in Newly Diagnosed, Peripheral T-Cell Lymphoma Not Recruiting

    Study of ONTAK and CHOP (chemotherapy drugs) to find out their ability to make Peripheral T-cell lymphoma disappear (for any period of time) and potentially lengthen life. The study will also compare what kind of side effects these drugs cause and how often they occur. The hypothesis is that patients with newly diagnosed peripheral T-Cell lymphoma, when given ONTAK + CHOP, will tolerate the treatment and will have a 20% improvement in response rate when compared to CHOP alone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lauren Pernicka, (650) 721 - 6977.

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  • A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for CD30-Positive Mature T-Cell and NK-Cell Neoplasms Not Recruiting

    The purpose of this study is to assess the safety profile of brentuximab vedotin sequentially and in combination with multi-agent chemotherapy in front-line treatment for CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma. It is a phase 1, open-label, dose escalation study in three arms designed to define the MTD, PK, immunogenicity, and anti-tumor activity of brentuximab vedotin in sequence and in combination with multi-agent front-line chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • A Phase 1 Dose Escalation Study of OMP-21M18 in Subjects With Solid Tumors Not Recruiting

    This is an open-label Phase 1 dose escalation study of OMP-21M18 in subjects with previously treated solid tumors for which there is no remaining standard curative therapy and no therapy with a demonstrated survival benefit. Up to 30 subjects will be enrolled at up to 4 centers. Subjects will be assessed for safety, immunogenicity, pharmacokinetics, biomarkers, and efficacy. No formal interim analyses will be performed. Prior to enrollment, subjects will undergo screening to determine study eligibility. Upon enrollment, subjects will receive weekly intravenous (IV) infusions of OMP-21M18 for 9 weeks. After 9 weeks of treatment, subjects will be assessed for disease status. If there is no evidence of disease progression or if the tumor is smaller, then subjects may continue to receive IV infusions of OMP-21M18 every other week until disease progression. Dose escalation will be conducted to determine the maximum tolerated dose (MTD). The dose levels of OMP 21M18 will be 0.5, 1.0, 2.5, 5, and 10 mg/kg administered IV weekly for 9 doses. No dose escalation or reduction will be allowed within a dose cohort. The dose may be administered at any time during the day. Three subjects will be treated at each dose level if no dose-limiting toxicities (DLTs) are observed. If 1 of 3 subjects experience a DLT, that dose level will be expanded to 6 subjects. If 2 or more subjects experience a DLT, no further subjects will be dosed at that level and 3 additional subjects will be added to the preceding dose cohort unless 6 subjects have already been treated at that dose level. Subjects will be assessed for DLTs from the time of the first dose through 7 days after administration of the 4th dose, but prior to administration of the 5th dose (i.e., Days 0-28). Dose escalation, if appropriate, will occur after all subjects in a cohort have completed their Day 28 DLT assessment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma Not Recruiting

    This phase II trial is studying how well sorafenib works in treating patients with recurrent diffuse large B-cell non-Hodgkin's lymphoma. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Daadi, (650) 725 - 6456.

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  • Combination Chemotherapy and Rituximab in Treating Patients With Untreated Mantle Cell Lymphoma Not Recruiting

    This phase II trial is studying how well giving rituximab together with combination chemotherapy and bortezomib works in treating patients with untreated mantle cell lymphoma. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving rituximab together with combination chemotherapy and bortezomib may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lauren Pernicka, (650) 721 - 6977.

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  • Chemotherapy Based on PET Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine, dacarbazine, cyclophosphamide, etoposide, procarbazine hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells. Comparing results of imaging procedures, such as PET scans and CT scans, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment. PURPOSE: This phase II clinical trial studies how well chemotherapy based on PET/CT scan works in treating patients with stage I or stage II Hodgkin lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Pitsiouni, (650) 721 - 6977.

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  • Rituximab in Treating Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known which rituximab regimen is more effective in treating indolent non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and comparing them to see how well they work in treating patients with low tumor burden indolent stage III non-Hodgkin's lymphoma or stage IV non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • Phase I/II of a CpG-Activated Whole Cell Vaccine Followed by Autologous Immunotransplant for MCL Recruiting

    While autologous hematopoietic stem cell transplant (AHCT) has been shown to cure some subtypes of non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL) still has a prognosis marked by relapse. This study will evaluate the safety and efficacy of treating newly diagnosed MCL patients with an autologous, tumor-derived vaccine followed by re-infusion of vaccine-primed T cells combined with standard autologous hematopoietic stem cell transplant (AHCT). CpG-MCL vaccine is derived from each patient's own tumor, treated in vitro with the immunostimulatory CpG-enriched oligodeoxynucleotide - PF-3512676 - and irradiated. The overall treatment schema is that patients receive: induction chemotherapy, priming vaccinations, leukapheresis to harvest vaccine-primed T cells, preparative myeloablative chemotherapy followed by AHCT, re-infusion of vaccine-primed T-cells ('immunotransplant') and repeat vaccinations zero and three months post-AHCT.

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  • Rituximab, Combination Chemotherapy, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage I or Stage II Non-Hodgkin's Lymphoma Not Recruiting

    This phase II trial is studying how well giving rituximab together with combination chemotherapy and yttrium Y 90 ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • A Single Agent Phase II Study of Romidepsin (Depsipeptide, FK228) in the Treatment of Cutaneous T-cell Lymphoma (CTCL) Not Recruiting

    GPI-04-0001 was a Phase II, non-randomized, open label, single arm study that was conducted at approximately 30 sites, primarily in the United States, Europe and Russia. It assessed the efficacy, safety, and tolerability of romidepsin as a treatment for cutaneous T-cell lymphoma (CTCL). Study patients (pts) received romidepsin in a dose of 14 mg/m^2 intravenously over 4 hours on Days 1, 8 and 15 of each 28-day cycle. The duration of study treatment was 6 cycles although pts who showed an objective response or stable disease could continue to receive therapy, at the discretion of the investigator, until disease progression or another withdrawal criterion was met.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sunil Arani Reddy, (650) 736 - 1234.

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  • Bevacizumab and Combination Chemotherapy in Treating Patients With Peripheral T-Cell Lymphoma or Natural Killer Cell Neoplasms Not Recruiting

    RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with several chemotherapy drugs (combination chemotherapy) works in treating patients with peripheral T-cell lymphoma or natural killer cell neoplasms.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Ahern, (650) 725 - 6413.

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  • A Dose and Schedule Finding Trial With AMG 531 for Chemotherapy Induced Thrombocytopenia (CIT) in Adults With Lymphoma Not Recruiting

    The purpose of this study is to identify a well-tolerated, effective dose and schedule of AMG 531 for the treatment of Chemotherapy Induced Thrombocytopenia (CIT) in subjects with lymphoma receiving multi-cycle chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • A Treatment-Option Study of Brentuximab Vedotin in Patients With Progression of Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma Not Recruiting

    The purpose of this study is to provide the option of brentuximab vedotin treatment to patients randomly allocated to placebo treatment in the Phase 3 study SGN35-005 that experienced disease progression of HL. Additionally in the US only, the purpose of this study is to provide access to brentuximab vedotin for patients with relapsed or refractory HL or patients with relapsed or refractory systemic ALCL who have previously failed frontline chemotherapy.

    Stanford is currently not accepting patients for this trial.

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  • A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL Not Recruiting

    This is a randomized trial to estimate the activity of R-ICE plus SGN-40 vs. R-ICE plus placebo in patients with DLBCL. The study will assess safety and tolerability and will measure any additional clinical benefit observed in patients receiving SGN-40.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • A Study of HGS1029 (AEG40826-2HCl) in Subjects With Advanced Solid Tumors Not Recruiting

    The purpose of this study is to evaluate the safety and tolerability of HGS1029 in subjects with advanced solid tumors and to determine a phase 2 dose.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Everolimus (RAD001) in Primary Therapy of Waldenstrom's Macroglobulinemia Not Recruiting

    The purpose of this research study is to determine the safety of RAD001(Everolimus) and the highest dose of this drug that can be given to people safely. RAD001(Everolimus) is a drug that works by preventing cells in the body from growing and dividing. Information from basic and Phase I clinical research studies suggests that RAD001 also may help to prevent tumor growth in people with relapsed or refractory lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Combination Chemotherapy Plus Low-Dose Radiation Therapy in Treating Patients With Stage I or Stage IIA Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with low-dose radiation therapy works in treating patients with stage I or stage IIA Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Anne Wiley, (650) 725 - 6432.

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  • A Study of DCDT2980S in Combination With MabThera/Rituxan or DCDS4501A in Combination With MabThera/Rituxan in Patients With Non-Hodgkin's Lymphoma Not Recruiting

    This randomized, multicenter, open-label study will evaluate the safety and the efficacy of DCDT2980S in combination with MabThera/Rituxan (rituximab) or DCDS4501A in combination with MabThera/Rituxan in patients with relapsed or refractory follicular non-Hodgkin's lymphoma and relapsed/refractory diffuse large B-cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, 650-736-2563.

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  • Phase 3 Frontline Therapy Trial in Patients With Advanced Classical Hodgkin Lymphoma Recruiting

    This open-label, randomized, 2-arm, multicenter, phase 3 study has the primary objective of comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin [Adriamycin], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin [Adriamycin],bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma(HL)

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  • Cyclosporine in Treating Patients With Recurrent or Refractory Angioimmunoblastic T-Cell Lymphoma Not Recruiting

    RATIONALE: Cyclosporine may help the immune system slow the growth of angioimmunoblastic T-cell lymphoma. PURPOSE: This phase II trial is studying how well cyclosporine works in treating patients with recurrent or refractory angioimmunoblastic T-cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • Study of Human Monoclonal Antibody to Treat Mycosis Fungoides and Sezary Syndrome Not Recruiting

    The purpose of this study is to determine the efficacy of the drug, HuMax-CD4, in patients with mycosis fungoides(MF) and sezary syndrome who are intolerant to or do not respond to treatment with Targretin® and one other standard therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Navi, (650) 736 - 2300.

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  • Genes in Predicting Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab and Combination Chemotherapy Not Recruiting

    RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients respond to treatment. PURPOSE: This phase II trial is studying how well genes and biomarkers predict outcome of patients with diffuse large B-cell lymphoma treated with rituximab and combination chemotherapy.

    Stanford is currently not accepting patients for this trial.

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  • Study of the Safety and Tolerability of PCI-32765 in Patients With Recurrent B Cell Lymphoma Not Recruiting

    The purpose of this study is to establish the safety and optimal dose of orally administered PCI-32765 in patients with recurrent B cell lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Spira Choudhury, (650) 736 - 2563.

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  • A Pivotal Open-Label Trial of Brentuximab Vedotin for Hodgkin Lymphoma Not Recruiting

    This is a single-arm, open-label, multicenter, pivotal clinical trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) as a single agent in patients with relapsed or refractory Hodgkin lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jonathan Euodia, (650) 725 - 6432.

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  • AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors Not Recruiting

    This is a multi-center, 2-part phase 1b/2 study of AMG 655 in combination with AMG 479 to be conducted in the United States and Spain. Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerable. Part 2 will evaluate the safety and estimate the efficacy of AMG 655 at the dose selected in Part 1 in combination with AMG 479 for the treatment of patients with advanced NSCLC (non-squamous histology; squamous histology), CRC, pancreatic cancer, ovarian cancer, and sarcoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Clinical Trial of PXD101 in Patients With T-Cell Lymphomas Not Recruiting

    This is an open-label, non-randomized trial to assess the effectiveness of PXD101 in patients with recurrent or refractory cutaneous or peripheral and other types of T-cell lymphomas. PXD101 is a new, potent histone deacetylase (HDAC) inhibitor. Patients are treated with belinostat(PXD101) 1000 mg/m2 on days 1-5 of a 21 day cycle.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Rituximab in Treating Patients With Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase II trial to study the effectiveness of rituximab in treating patients who have Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Daadi, (650) 725 - 6456.

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  • A Randomized Phase II Study of Oral Sapacitabine in Patients With Advanced Cutaneous T-cell Lymphoma Not Recruiting

    This is an open label, randomized phase II study designed to evaluate the tolerability and response rate of high-dose and low-dose regimens in patients with advanced cutaneous T-cell lymphoma (CTCL) who have had progressive, recurrent, or persistent disease on or following 2 systemic therapies.

    Stanford is currently not accepting patients for this trial. For more information, please contact Daniel Navi, (650) 736 - 2300.

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  • Phase II Study of Bexxar in Relapsed/Refractory Diffuse Large Cell Lymphoma Not Recruiting

    The purpose of this study is to obtain safety and efficacy data using tositumomab or Bexxar in patients with relapsed/refractory diffuse large cell Non-Hodgkin's lymphoma (DLCL).

    Stanford is currently not accepting patients for this trial. For more information, please contact Lucy Schoen, (650) 725 - 1718.

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  • A Study of the Safety and Pharmacokinetics of Escalating Doses of DCDT2980S in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia And DCDT2980S in Combination With Rituximab in Patients With Relapsed or Refractory B-Cell Non Hodgkin's Lymphoma Not Recruiting

    This is a Phase I, multicenter, open-label, dose-escalation study of DCDT2980S administered by intravenous (IV) infusion to patients with relapsed or refractory hematologic malignancies. In addition, at selected sites, DCDT2980S will be studied in combination with rituximab.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • An SGN-35 Trial for Patients Who Have Previously Participated in an SGN-35 Study Not Recruiting

    This is a multicenter, open-label study to evaluate the safety and efficacy of treatment with SGN-35 in patients who have previously participated in an SGN-35 study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Safety, Pharmacodynamics (PD), Pharmacokinetics (PK) Study of SHP141 in 1A, 1B, or 2A Cutaneous T-Cell Lymphoma (CTCL) Recruiting

    The purpose of this study is to investigate the safety and tolerability of topical SHP141 applied directly to skin lesions in patients with Stage IA, IB, or IIA Cutaneous T-cell Lymphoma. This study will also investigate the effect of SHP141 on skin lesions in patients with Stage IA, IB, or IIA CTCL.

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  • A Study of CDX-1127 in Patients With Select Solid Tumor Types or Hematologic Cancers Recruiting

    This is a study of CDX-1127, a therapy that targets the immune system and may act to promote anti-cancer effects. The study enrolls patients with hematologic cancers (certain leukemias and lymphomas), as well as patients with select types of solid tumors.

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  • A Study of Escalating Doses of DCDS4501A in Patients With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukemia and DCDS4501A in Combination With Rituximab in Patients With Relapsed or Refractory B-Cell Non-Hodgkins Lymphoma Not Recruiting

    This is a Phase I, multicenter, open-label, dose-escalation study of DCDS4501A administered as a single agent by IV infusion to patients with relapsed or refractory hematologic malignancies. In Phase Ib, patients will receive DCDS4501A in combination with rituximab.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Ibrutinib (PCI-32765) in Waldenstrom's Macroglobulinemia Not Recruiting

    This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug, PCI-32765, to learn whether PCI-32765 works in treating a specific cancer. "Investigational" means that PCI-32765 is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if PCI-32765 is effective for treating different types of cancer. It also means that the FDA has not yet approved PCI-32765 for use in patients, including people with Waldenstrom's Macroglobulinemia. PCI-32765 is a newly discovered drug that is being developed as an anti-cancer agent. PCI-32765 is a Bruton's tyrosine kinase (Btk) inhibitor drug which interrupts B cell receptor (BCR) signaling in lymphomas by selectively and irreversibly binding to the Btk protein, which then results in malignant cell death. This drug has been used in laboratory experiments and other research studies in B-cell malignancies and information from those other research studies suggests that PCI-32765 may be a treatment strategy for B-cell malignancies, including Waldenstrom's Macroglobulinemia. In this research study, the investigators are testing the safety and efficacy of PCI-32765 as a treatment option for relapsed or refractory Waldenstrom's Macroglobulinemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dina Chinichian, (650) 725 - 6432.

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  • Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma Recruiting

    RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma. PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.

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  • A Study of Pharmacokinetic Drug Interaction Study of the Hedgehog Pathway Inhibitor GDC-0449 in Combination With Rosiglitazone or Combined Oral Contraceptive in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists Not Recruiting

    This is a single-arm, multicenter, Phase Ib study designed to describe the effect of GDC-0449 on the pharmacokinetics of rosiglitazone and oral contraceptives in patients with advanced solid tumors who are refractory to treatment or for whom no standard therapy exists.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ruth Lira, (650) 723 - 1367.

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  • Safety and Efficacy Study of Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma Not Recruiting

    The purpose of this study is to evaluate the efficacy of PCI-32765 in relapsed/refractory de novo activated B-cell (ABC) and germinal-cell B-Cell (GCB) Diffuse Large B-cell Lymphoma (DLBCL).

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Study of Cabozantinib (XL184) in Adults With Advanced Malignancies Not Recruiting

    The purpose of this study is to determine whether or not XL184 demonstrates anti-tumor activity in selected tumor types under a randomized discontinuation trial (RDT) design. Subjects who have responded to study drug after 12 weeks of open-label XL184 administration will continue to take XL184. Subjects who are clearly progressing will discontinue study treatment and subjects who demonstrate stable disease will be randomized to either XL184 or placebo. For individual patients, once disease progression is observed, the blind will be broken and subjects who were randomized to placebo will be offered the option to receive open-label XL184. Subjects who progressed while taking XL184 will discontinue study treatment. Emerging data may support enrollment in an open-label, non-randomized expansion cohort (NRE). There will be NRE cohorts for prostate and ovarian cancers.

    Stanford is currently not accepting patients for this trial. For more information, please contact Dana Supan, (650) 736 - 1694.

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  • Study of Pralatrexate in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma Not Recruiting

    This study is being conducted to identify how much and how often pralatrexate, given with vitamin B12 and folic acid, can be given safely to patients with cutaneous T-cell lymphoma (CTCL) that has relapsed (returned after responding to previous treatment) or is refractory (has not responded to previous treatment). It is also being conducted to get information on whether or not pralatrexate is effective in treating relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

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  • Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL Recruiting

    The purpose of this study is to compare the progression free survival of KW-0761 versus vorinostat for subjects with relapsed or refractory CTCL.

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  • Phase II Total Skin Electron Beam Therapy (TSEBT 12 Gy) in Stage IB-IIIA Mycosis Fungoides Not Recruiting

    To examine the efficacy and safety of total skin electron beam therapy to a dose of 12 Gray (TSEBT 12 Gy) in patients who have mycosis fungoides (MF) staged as IB to IIIA.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cameron Harrison, (650) 721 - 7186.

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  • Forodesine in the Treatment of Cutaneous T-Cell Lymphoma Not Recruiting

    This is a Phase II, non-randomized, open-label, single-arm trial that will be conducted at up to 50 sites in North America, Europe and Australia. This study is designed to assess objective response (OR) [complete response (CR) or partial response (PR)] in subjects with cutaneous manifestations of CTCL with a requirement for maintenance of such objective response for at least 28 days in subjects with stage IIB, III, and IVA CTCL. Additionally, this study will evaluate the safety and tolerability of CTCL subjects Stages IB, IIA, IIB, III, or IVA treated with oral forodesine.

    Stanford is currently not accepting patients for this trial. For more information, please contact Natalie Viakhireva, (650) 723 - 8949.

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  • Study of Bexxar Combined With External Beam Radiation Therapy for Patients With Relapsed, Bulky Non-Hodgkin's Lymphoma Not Recruiting

    We hope to learn whether I-131 tositumomab combined with external beam radiation therapy is an effective means of treating relapsed, bulky non-Hodgkin's lymphoma. The purpose of the study is to determine the overall response rate with responses described as: Site-dependent and overall CR and functional CR (CR of CRu(Complete Response Unconfirmed)/PR with PET negativity), or PR rates.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lucy Schoen, (650) 725 - 1718.

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  • Assessing Response to Treatment in Non-Hodgkin's Lymphoma Patients Using 64Cu-DOTA-Rituximab PET/CT Not Recruiting

    Rituximab is an antibody targeted against the CD20 antigen found primarily on B-cells. Therefore, an imaging agent targeting CD20 expression may provide a more accurate evaluation of extent of disease and response to therapy than the current standard of care, F-18 FDG PET/CT. The main purpose of the study is to investigate a new PET/CT imaging probe for detection and follow up of lymphoma. Following are the 3 aims of the study: a) Phase I testing in lymphoma patients of Cu-64 labelled Rituxan for defining normal tracer biodistribution, stability, pharmacokinetics and radiation dosimetry; b) comparison of Cu-64 Rituxan and F-18 FDG PET/CT in lymphoma patients; c) evaluation of changes in uptake of Cu-64 Rituxan in response to rituximab-based treatment in CD20-positive B-cell NHL

    Stanford is currently not accepting patients for this trial. For more information, please contact Lindee Burton, (650) 725 - 4712.

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  • Safety and Efficacy of RAD001 in Patients With Mantle Cell Lymphoma Who Are Refractory or Intolerant to Velcade® Therapy. Not Recruiting

    This study is to evaluate the safety and efficacy of a daily, oral dose of 10 mg RAD001 in patients with Mantle Cell Lymphoma who are refractory or intolerant to Velcade® therapy and who have received at least one prior antineoplastic agent other than Velcade®, either separately or in combination with Velcade® (see inclusion criteria). Intolerance to Velcade® therapy is determined by the study investigator based on clinical evaluations. Patients are considered refractory to Velcade® if they have documented radiological progression on or within 12 months of the last dose of Velcade® when given alone or, on or within 12 months of the last dose of the last component of a combination therapy which included Velcade®.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, (650) 736 - 2563.

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  • Extension Study in Subjects Who Relapsed After Complete Response on Study KW-0761-001 Not Recruiting

    This study will enroll subjects with either Peripheral T-Cell Lymphoma (PTCL) or Cutaneous T-Cell Lymphoma(CTCL),including mycosis fungoides (MF) and Sezary Syndrome (SS), who have relapsed after achieving a complete response in study, KW-0761-001.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, (650) 421 - 6370.

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  • An Open Label Study to Evaluate the Safety and Efficacy of Mechlorethamine(MCH) 0.04% Formulation in Mycosis Fungoides Not Recruiting

    To evaluate the efficacy and safety of topical application of MCH 0.04% in a propylene glycol ointment (PG)in patients with stage I or IIA MF previously treated with MCH 0.02% in a PG or AP ointment who did not achieve a complete response.

    Stanford is currently not accepting patients for this trial. For more information, please contact Kokil Bakshi, (650) 421 - 6370.

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  • Pralatrexate and Bexarotene in Patients With Relapsed or Refractory Cutaneous T-cell Lymphoma Not Recruiting

    This study is designed to determine the recommended dose, safety, pharmacokinetics, and early efficacy of the combination of pralatrexate plus oral bexarotene in patients with relapsed or refractory CTCL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cutaneous Lymphoma Coordinator, (650) 421 - 6370.

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  • Ph II of Non-myeloablative Allogeneic Transplantation Using TLI & ATG In Patients w/ Cutaneous T Cell Lymphoma Recruiting

    Non-myeloablative approach for allogeneic transplant is a reasonable option, especially given that the median age at diagnosis is 55-60 years and frequently present compromised skin in these patients, which increases the risk of infection. Therefore, we propose a clinical study with allogeneic HSCT using a unique non-myeloablative preparative regimen, TLI/ATG, to treat advanced MF/SS.

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  • Safety and Tolerability Study of PCI-32765 in B Cell Lymphoma and Chronic Lymphocytic Leukemia Recruiting

    The purpose of this study is to determine the long-term safety of a fixed-dose, daily regimen of PCI-32765 PO in subjects with B cell lymphoma or chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL).

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  • A Study of PCI-32765 (Ibrutinib) in Patients With Refractory Follicular Lymphoma Not Recruiting

    The purpose of this study is to evaluate the efficacy and safety of PCI-32765 (ibrutinib) administered to patients with chemoimmunotherapy-resistant follicular lymphoma (FL).

    Stanford is currently not accepting patients for this trial. For more information, please contact Lori Richards, 650-725-8589.

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  • Brentuximab Vedotin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Stage II-IV Hodgkin Lymphoma Recruiting

    This phase II trial studies how well giving brentuximab vedotin together with combination chemotherapy works in treating older patients with previously untreated stage II-IV Hodgkin lymphoma (HL). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine (AVD), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin, doxorubicin hydrochloride, vinblastine, and dacarbazine together may kill more cancer cells.

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  • An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma Not Recruiting

    The purpose of this study is to provide patients who have relapsed or refractory Mantle Cell Lymphoma (MCL) with early access to an investigational medication called ibrutinib (PCI-32765) and to collect safety information about the drug.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, 650-736-2563.

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  • A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma Recruiting

    The purpose of this study is to evaluate the efficacy and safety of ibrutinib given in combination with bendamustine and rituximab in patients 65 years of age or older with newly diagnosed mantle cell lymphoma.

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  • ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas Recruiting

    This is a double-blind, randomized, multicenter, phase 3 clinical trial to compare the efficacy and safety of brentuximab vedotin in combination with CHP with the standard-of-care CHOP in patients with CD30-positive mature T-cell lymphomas.

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  • Study of Brentuximab Vedotin Combined With Bendamustine in Patients With Hodgkin Lymphoma Recruiting

    The purpose of this study is to assess safety and efficacy of brentuximab vedotin in combination with bendamustine in patients with relapsed or refractory Hodgkin lymphoma. It is an open-label, 2-stage study designed to determine the recommended dose level of bendamustine in combination with brentuximab vedotin. The study will assess the safety profile of the combination treatment and determine what proportion of patients achieve a complete remission.

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  • Prospective Collection of Data in Patients With Peripheral T-Cell Lymphoma Recruiting

    The designed study follows up the retrospective previous one by the International T-cell Non-Hodgkin's Lymphoma Study Group. It is designed as a prospective collection of information potentially useful to predict the prognosis of newly diagnosed patients with the more frequent subtypes of Peripheral T-cell lymphoma (Peripheral T-cell lymphoma unspecified and Angioimmunoblastic T-cell lymphoma) and to better define clinical characteristics and outcome of the more uncommon subtypes

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  • A Safety Study of SGN-CD19A for B-Cell Lymphoma Recruiting

    This is a phase 1, open-label, dose-escalation, multicenter study to evaluate the safety and tolerability of SGN-CD19A in patients with relapsed or refractory B-lineage non-Hodgkin lymphoma (B-NHL)

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Teaching

2013-14 Courses


Postdoctoral Advisees


Graduate and Fellowship Programs


Publications

Journal Articles


  • Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience. Blood Tan, D., Horning, S. J., Hoppe, R. T., Levy, R., Rosenberg, S. A., Sigal, B. M., Warnke, R. A., Natkunam, Y., Han, S. S., Yuen, A., Plevritis, S. K., Advani, R. H. 2013; 122 (6): 981-987

    Abstract

    Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1-2 FL referred from 1960-2003 and treated at Stanford were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n=180); era 2, anthracycline (1976-1986, n=426), era 3, aggressive chemotherapy/purine analogs (1987-1996, n=471) and era 4, rituximab (1997-2003, n=257). Clinical characteristics, patterns of care and survival outcomes were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at time of diagnosis. The median OS was 13.6 years. Age, gender and stage did not differ across the eras. Although primary treatment varied, event free survival after the first treatment did not differ between eras (p=0.17). Median OS improved from approximately 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (p<0.001) with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same time period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement.

    View details for DOI 10.1182/blood-2013-03-491514

    View details for PubMedID 23777769

  • Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma NEW ENGLAND JOURNAL OF MEDICINE Wang, M. L., Rule, S., Martin, P., Goy, A., Auer, R., Kahl, B. S., Jurczak, W., Advani, R. H., Romaguera, J. E., Williams, M. E., Barrientos, J. C., Chmielowska, E., Radford, J., Stilgenbauer, S., Dreyling, M., Jedrzejczak, W. W., Johnson, P., Spurgeon, S. E., Li, L., Zhang, L., Newberry, K., Ou, Z., Cheng, N., Fang, B., McGreivy, J., Clow, F., Buggy, J. J., Chang, B. Y., Beaupre, D. M., Kunkel, L. A., Blum, K. A. 2013; 369 (6): 507-516

    Abstract

    Bruton's tyrosine kinase (BTK) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin's lymphoma, including mantle-cell lymphoma.In this phase 2 study, we investigated oral ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma. Patients were enrolled into two groups: those who had previously received at least 2 cycles of bortezomib therapy and those who had received less than 2 complete cycles of bortezomib or had received no prior bortezomib therapy. The primary end point was the overall response rate. Secondary end points were duration of response, progression-free survival, overall survival, and safety.The median age was 68 years, and 86% of patients had intermediate-risk or high-risk mantle-cell lymphoma according to clinical prognostic factors. Patients had received a median of three prior therapies. The most common treatment-related adverse events were mild or moderate diarrhea, fatigue, and nausea. Grade 3 or higher hematologic events were infrequent and included neutropenia (in 16% of patients), thrombocytopenia (in 11%), and anemia (in 10%). A response rate of 68% (75 patients) was observed, with a complete response rate of 21% and a partial response rate of 47%; prior treatment with bortezomib had no effect on the response rate. With an estimated median follow-up of 15.3 months, the estimated median response duration was 17.5 months (95% confidence interval [CI], 15.8 to not reached), the estimated median progression-free survival was 13.9 months (95% CI, 7.0 to not reached), and the median overall survival was not reached. The estimated rate of overall survival was 58% at 18 months.Ibrutinib shows durable single-agent efficacy in relapsed or refractory mantle-cell lymphoma. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01236391.)

    View details for DOI 10.1056/NEJMoa1306220

    View details for Web of Science ID 000322842000007

    View details for PubMedID 23782157

  • Targeted Therapy in Relapsed Classical Hodgkin Lymphoma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Dinner, S., Advani, R. 2013; 11 (8): 968-976

    Abstract

    Although frontline treatment of advanced Hodgkin lymphoma (HL) produces high cure rates, disease either will not respond to or will relapse after initial therapy in approximately a quarter of patients. Many patients with disease relapse can be successfully salvaged with second-line chemotherapy followed by autologous stem cell transplantation (ASCT). Patients whose disease relapses after ASCT are rarely cured. A unique pathophysiologic feature of HL is that the malignant Reed-Sternberg (HRS) cell is rare and resides within a microenvironment of inflammatory and immune-related cells. The recent FDA approval of the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) for patients with either primary refractory HL or those whose disease relapses after ASCT represents a major advance in therapy. This article focuses on BV and other novel agents that target the HRS cell surface, intracellular signaling pathways, and tumor microenvironment.

    View details for Web of Science ID 000323156900007

    View details for PubMedID 23946175

  • Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial. Blood Kanakry, J. A., Li, H., Gellert, L. L., Lemas, M. V., Hsieh, W., Hong, F., Tan, K. L., Gascoyne, R. D., Gordon, L. I., Fisher, R. I., Bartlett, N. L., Stiff, P., Cheson, B. D., Advani, R., Miller, T. P., Kahl, B. S., Horning, S. J., Ambinder, R. F. 2013; 121 (18): 3547-3553

    Abstract

    Epstein-Barr virus (EBV) is associated with Hodgkin lymphoma (HL) and can be detected by in situ hybridization (ISH) of viral nucleic acid (EBER) in tumor cells. We sought to determine whether plasma EBV-DNA could serve as a surrogate for EBER-ISH and to explore its prognostic utility in HL. Specimens from the Cancer Cooperative Intergroup Trial E2496 were used to compare pretreatment plasma EBV-DNA quantification with EBV tumor status by EBER-ISH. A cutoff of >60 viral copies/100 µL plasma yielded 96% concordance with EBER-ISH. Pretreatment and month 6 plasma specimens were designated EBV(-) or EBV(+) by this cutoff. Patients with pretreatment EBV(+) plasma (n = 54) had inferior failure-free survival (FFS) compared with those with pretreatment EBV(-) plasma (n = 274), log-rank P = .009. By contrast, no difference in FFS was observed when patients were stratified by EBER-ISH. Pretreatment plasma EBV positivity was an independent predictor of treatment failure on multivariate analyses. At month 6, plasma EBV(+) patients (n = 7) had inferior FFS compared with plasma EBV(-) patients (n = 125), log-rank P = .007. These results confirm that plasma EBV-DNA is highly concordant with EBER-ISH in HL and suggest that it may have prognostic utility both at baseline and after therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003389.

    View details for DOI 10.1182/blood-2012-09-454694

    View details for PubMedID 23386127

  • Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma NEW ENGLAND JOURNAL OF MEDICINE Dunleavy, K., Pittaluga, S., Maeda, L. S., Advani, R., Chen, C. C., Hessler, J., Steinberg, S. M., Grant, C., Wright, G., Varma, G., Staudt, L. M., Jaffe, E. S., Wilson, W. H. 2013; 368 (15): 1408-1416

    Abstract

    Primary mediastinal B-cell lymphoma is a distinct subtype of diffuse large-B-cell lymphoma that is closely related to nodular sclerosing Hodgkin's lymphoma. Patients are usually young and present with large mediastinal masses. There is no standard treatment, but the inadequacy of immunochemotherapy alone has resulted in routine consolidation with mediastinal radiotherapy, which has potentially serious late effects. We aimed to develop a strategy that improves the rate of cure and obviates the need for radiotherapy.We conducted a single-group, phase 2, prospective study of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) and filgrastim without radiotherapy in 51 patients with untreated primary mediastinal B-cell lymphoma. We used results from a retrospective study of DA-EPOCH-R from another center to independently verify the outcomes.The patients had a median age of 30 years (range, 19 to 52) and a median tumor diameter of 11 cm; 59% were women. During a median of 5 years of follow-up, the event-free survival rate was 93%, and the overall survival rate was 97%. Among the 16 patients who were involved in the retrospective analysis at another center, over a median of 3 years of follow-up, the event-free survival rate was 100%, and no patients received radiotherapy. No late morbidity or cardiac toxic effects were found in any patients. After follow-up ranging from 10 months to 14 years, all but 2 of the 51 patients (4%) who received DA-EPOCH-R alone were in complete remission. The 2 remaining patients received radiotherapy and were disease-free at follow-up.Therapy with DA-EPOCH-R obviated the need for radiotherapy in patients with primary mediastinal B-cell lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00001337.).

    View details for DOI 10.1056/NEJMoa1214561

    View details for Web of Science ID 000317333600008

    View details for PubMedID 23574119

  • Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial ANNALS OF ONCOLOGY Advani, R. H., Hoppe, R. T., Baer, D., Mason, J., Warnke, R., Allen, J., Daadi, S., Rosenberg, S. A., Horning, S. J. 2013; 24 (4): 1044-1048

    Abstract

    To assess the efficacy of an abbreviated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS: with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the G4 study. Stanford V chemotherapy was administered for 8 weeks followed by radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated.All 87 enrolled patients completed the abbreviated regimen. At a median follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively. Therapy was well tolerated with no treatment-related deaths.Mature results of the abbreviated Stanford V regimen in nonbulky early-stage HL are excellent and comparable to the results from other contemporary therapies.

    View details for DOI 10.1093/annonc/mds542

    View details for Web of Science ID 000316701300027

    View details for PubMedID 23136225

  • The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496 BRITISH JOURNAL OF HAEMATOLOGY Evens, A. M., Hong, F., Gordon, L. I., Fisher, R. I., Bartlett, N. L., Connors, J. M., Gascoyne, R. D., Wagner, H., Gospodarowicz, M., Cheson, B. D., Stiff, P. J., Advani, R., Miller, T. P., Hoppe, R. T., Kahl, B. S., Horning, S. J. 2013; 161 (1): 76-86

    Abstract

    There is a lack of contemporary prospective data examining the adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) and Stanford V (SV; doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone) regimens in older Hodgkin lymphoma (HL) patients. Forty-four advanced-stage, older HL patients (aged ?60 years) were treated on the randomized study, E2496. Toxicities were mostly similar between chemotherapy regimens, although 24% of older patients developed bleomycin lung toxicity (BLT), which occurred mainly with ABVD (91%). Further, the BLT-related mortality rate was 18%. The overall treatment-related mortality for older HL patients was 9% vs. 0·3% for patients aged <60 years (P < 0·001). Among older patients, there were no survival differences between ABVD and SV. According to age, outcomes were significantly inferior for older versus younger patients (5-year failure-free survival: 48% vs. 74%, respectively, P = 0·002; 5-year overall survival: 58% and 90%, respectively, P < 0·0001), although time-to-progression (TTP) was not significantly different (5-year TTP: 68% vs. 78%, respectively, P = 0·37). Furthermore, considering progression and death without progression as competing risks, the risk of progression was not different between older and younger HL patients (5 years: 30% and 23%, respectively, P = 0·30); however, the incidence of death without progression was significantly increased for older HL patients (22% vs. 9%, respectively, P < 0·0001). Altogether, the marked HL age-dependent survival differences appeared attributable primarily to non-HL events.

    View details for DOI 10.1111/bjh.12222

    View details for Web of Science ID 000316333300009

    View details for PubMedID 23356491

  • Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496) JOURNAL OF CLINICAL ONCOLOGY Gordon, L. I., Hong, F., Fisher, R. I., Bartlett, N. L., Connors, J. M., Gascoyne, R. D., Wagner, H., Stiff, P. J., Cheson, B. D., Gospodarowicz, M., Advani, R., Kahl, B. S., Friedberg, J. W., Blum, K. A., Habermann, T. M., Tuscano, J. M., Hoppe, R. T., Horning, S. J. 2013; 31 (6): 684-691

    Abstract

    Although ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been established as the standard of care in patients with advanced Hodgkin lymphoma, newer regimens have been investigated, which have appeared superior in early phase II studies. Our aim was to determine if failure-free survival was superior in patients treated with the Stanford V regimen compared with ABVD.The Eastern Cooperative Oncology Group, along with the Cancer and Leukemia Group B, the Southwest Oncology Group, and the Canadian NCIC Clinical Trials Group, conducted this randomized phase III trial in patients with advanced Hodgkin lymphoma. Stratification factors included extent of disease (localized v extensive) and International Prognostic Factors Project Score (0 to 2 v 3 to 7). The primary end point was failure-free survival (FFS), defined as the time from random assignment to progression, relapse, or death, whichever occurred first. Overall survival, a secondary end point, was measured from random assignment to death as a result of any cause. This design provided 87% power to detect a 33% reduction in FFS hazard rate, or a difference in 5-year FFS of 64% versus 74% at two-sided .05 significance level.There was no significant difference in the overall response rate between the two arms, with complete remission and clinical complete remission rates of 73% for ABVD and 69% for Stanford V. At a median follow-up of 6.4 years, there was no difference in FFS: 74% for ABVD and 71% for Stanford V at 5 years (P = .32).ABVD remains the standard of care for patients with advanced Hodgkin lymphoma.

    View details for DOI 10.1200/JCO.2012.43.4803

    View details for Web of Science ID 000315086400016

    View details for PubMedID 23182987

  • Risk of Therapy-Related Secondary Leukemia in Hodgkin Lymphoma: The Stanford University Experience Over Three Generations of Clinical Trials JOURNAL OF CLINICAL ONCOLOGY Koontz, M. Z., Horning, S. J., Balise, R., Greenberg, P. L., Rosenberg, S. A., Hoppe, R. T., Advani, R. H. 2013; 31 (5): 592-598

    Abstract

    To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).

    View details for DOI 10.1200/JCO.2012.44.5791

    View details for Web of Science ID 000314820400017

    View details for PubMedID 23295809

  • Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma BLOOD Rubenstein, J. L., Li, J., Chen, L., Advani, R., Drappatz, J., Gerstner, E., Batchelor, T., Krouwer, H., Hwang, J., Auerback, G., Kadoch, C., Lowell, C., Munster, P., Cha, S., Shuman, M. A., Damon, L. E. 2013; 121 (5): 745-751

    Abstract

    Recurrent CNS lymphoma continues to be associated with poor outcomes in the rituximab era. Although IV rituximab mediates superior disease control of systemic non-Hodgkin lymphoma (NHL), it fails to completely eliminate the risk of meningeal recurrence, likely due to minimal CNS penetration. Given that rituximab acts synergistically with chemotherapy, we conducted the first phase 1 study of intraventricular immunochemotherapy in patients with recurrent CNS NHL. Fourteen patients received 10 mg or 25 mg intraventricular rituximab twice weekly for 4 weeks, with rituximab administered as monotherapy during the first treatment each week and rituximab administered in combination with methotrexate (MTX) during the second treatment each week. More than 150 doses were administered without serious toxicity. In a population with high-refractory CNS NHL, 75% of patients achieved complete cytologic responses and 43% achieved an overall complete response in CSF and/or brain parenchyma. Two patients achieved a first complete response of CNS NHL with intraventricular rituximab/MTX, including 1 with CNS lymphoma refractory to high-dose systemic and intrathecal MTX plus IV rituximab. We conclude that intraventricular rituximab in combination with MTX is feasible and highly active in the treatment of drug-resistant CNS NHL that is refractory or unresponsive to IV rituximab.Phase I study showed that intraventricular rituximab plus methotrexate is feasible and active in the treatment of refractory CNS lymphoma.

    View details for DOI 10.1182/blood-2012-07-440974

    View details for Web of Science ID 000314867200007

    View details for PubMedID 23197589

  • Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies JOURNAL OF CLINICAL ONCOLOGY Advani, R. H., Buggy, J. J., Sharman, J. P., Smith, S. M., Boyd, T. E., Grant, B., Kolibaba, K. S., Furman, R. R., Rodriguez, S., Chang, B. Y., Sukbuntherng, J., Izumi, R., Hamdy, A., Hedrick, E., Fowler, N. H. 2013; 31 (1): 88-94

    Abstract

    Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies.Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles.Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months.Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.

    View details for DOI 10.1200/JCO.2012.42.7906

    View details for Web of Science ID 000312911900021

    View details for PubMedID 23045577

  • Tumor-associated macrophages predict inferior outcomes in classic Hodgkin lymphoma: a correlative study from the E2496 Intergroup trial BLOOD Tan, K. L., Scott, D. W., Hong, F., Kahl, B. S., Fisher, R. I., Bartlett, N. L., Advani, R. H., Buckstein, R., Rimsza, L. M., Connors, J. M., Steidl, C., Gordon, L. I., Horning, S. J., Gascoyne, R. D. 2012; 120 (16): 3280-3287

    Abstract

    Increased tumor-associated macrophages (TAMs) are reported to be associated with poor prognosis in classic Hodgkin lymphoma (CHL). We investigated the prognostic significance of TAMs in the E2496 Intergroup trial, a multicenter phase 3 randomized controlled trial comparing ABVD and Stanford V chemotherapy in locally extensive and advanced stage CHL. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tumor tissue and included 287 patients. Patients were randomly assigned into training (n = 143) and validation (n = 144) cohorts. Immunohistochemistry for CD68 and CD163, and in situ hybridization for EBV-encoded RNA were performed. CD68 and CD163 IHC were analyzed by computer image analysis; optimum thresholds for overall survival (OS) were determined in the training cohort and tested in the independent validation cohort. Increased CD68 and CD163 expression was significantly associated with inferior failure-free survival and OS in the validation cohort. Increased CD68 and CD163 expression was associated with increased age, EBV-encoded RNA positivity, and mixed cellularity subtype of CHL. Multivariate analysis in the validation cohort showed increased CD68 or CD163 expression to be significant independent predictors of inferior failure-free survival and OS. We demonstrate the prognostic significance of TAMs in locally extensive and advanced-stage CHL in a multicenter phase 3 randomized controlled clinical trial.

    View details for DOI 10.1182/blood-2012-04-421057

    View details for Web of Science ID 000311619200019

    View details for PubMedID 22948049

  • Phase II Study of Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Immunochemotherapy Followed by Yttrium-90-Ibritumomab Tiuxetan in Untreated Mantle-Cell Lymphoma: Eastern Cooperative Oncology Group Study E1499 JOURNAL OF CLINICAL ONCOLOGY Smith, M. R., Li, H., Gordon, L., Gascoyne, R. D., Paietta, E., Forero-Torres, A., Kahl, B. S., Advani, R., Hong, F., Horning, S. J. 2012; 30 (25): 3119-3126

    Abstract

    To test the hypothesis that consolidation therapy with yttrium-90 ((90)Y) -ibritumomab tiuxetan after brief initial therapy with four cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated mantle-cell lymphoma would be a well-tolerated regimen that would improve outcomes compared with historical R-CHOP data.Patients ? 18 years old with histologically confirmed mantle-cell lymphoma expressing CD20 and cyclin D1 who had not received any previous therapy and had an Eastern Cooperative Oncology Group performance status of 0 to 2 and adequate organ function were eligible. The study enrolled and treated 57 patients, of whom 56 patients were eligible. Fifty-two patients (50 eligible patients) received (90)Y-ibritumomab tiuxetan. The study design required 52 eligible patients to detect a 50% improvement in the median time to treatment failure (TTF) compared with that reported for six cycles of R-CHOP.With 56 analyzed patients (median age, 60 years; men, 73%), the overall response rate was 82% (55% complete response/complete response-unconfirmed). With a median follow-up of 72 months, the median TTF was 34.2 months. The median overall survival (OS) has not been reached, with an estimated 5-year OS of 73% (79% for patients ? age 65 years v 62% for patients > age 65 years; P = .08 [log-rank test]). There were no unexpected toxicities.R-CHOP given for four cycles followed by (90)Y-ibritumomab tiuxetan compared favorably with historical results with six cycles of R-CHOP in patients with previously untreated mantle-cell lymphoma. This regimen was well tolerated and should be applicable to most patients with this disease.

    View details for DOI 10.1200/JCO.2012.42.2444

    View details for Web of Science ID 000308558800018

    View details for PubMedID 22851557

  • Brentuximab Vedotin in Transplant-Naive Patients with Relapsed or Refractory Hodgkin Lymphoma: Analysis of Two Phase I Studies ONCOLOGIST Forero-Torres, A., Fanale, M., Advani, R., Bartlett, N. L., Rosenblatt, J. D., Kennedy, D. A., Younes, A. 2012; 17 (8): 1073-1080

    Abstract

    Brentuximab vedotin is an antibody-drug conjugate designed to selectively deliver monomethyl auristatin E, a microtubule-disrupting agent, to CD30-expressing cells. Brentuximab vedotin induces durable objective responses in patients with relapsed or refractory Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). The objective of this post-hoc analysis was to characterize the safety and efficacy of brentuximab vedotin for patients with relapsed or refractory HL who refused or were ineligible for ASCT.This case series included 20 transplant-naïve patients who were enrolled in two phase I multicenter studies. Patients received brentuximab vedotin intravenously every 3 weeks or every week for 3 out of 4 weeks.The majority of patients were transplant-naïve because of chemorefractory disease. Median age was 31.5 years (range, 12-87 years). Treatment-emergent adverse events in >20% of patients were peripheral neuropathy, fatigue, nausea, pyrexia, diarrhea, weight decreased, anemia, back pain, decreased appetite, night sweats, and vomiting; most events were grade 1 or 2. Six patients obtained objective responses: two complete remissions and four partial remissions. Median duration of response was not met; censored durations ranged from >6.8 to >13.8 months. Three of six responders subsequently received ASCT.Brentuximab vedotin was associated with manageable adverse events in transplant-naïve patients with relapsed or refractory HL. The objective responses observed demonstrate that antitumor activity is not limited to patients who received brentuximab vedotin after ASCT. The promising activity observed in this population warrants further study.

    View details for DOI 10.1634/theoncologist.2012-0133

    View details for Web of Science ID 000308126100010

    View details for PubMedID 22855426

  • Brentuximab Vedotin (SGN-35) in Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma: Results of a Phase II Study JOURNAL OF CLINICAL ONCOLOGY Pro, B., Advani, R., Brice, P., Bartlett, N. L., Rosenblatt, J. D., Illidge, T., Matous, J., Ramchandren, R., Fanale, M., Connors, J. M., Yang, Y., Sievers, E. L., Kennedy, D. A., Shustov, A. 2012; 30 (18): 2190-2196

    Abstract

    Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive subtype of T-cell lymphoma characterized by the uniform expression of CD30. The antibody-drug conjugate brentuximab vedotin delivers the potent antimicrotubule agent monomethylauristatin E to CD30-positive malignant cells. A phase II multicenter trial was conducted to evaluate the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory systemic ALCL.Patients with systemic ALCL and recurrent disease after at least one prior therapy received brentuximab vedotin 1.8 mg/kg intravenously every 3 weeks over 30 minutes as an outpatient infusion. The primary end point of the study was overall objective response rate as assessed by independent central review.Of 58 patients treated in the study, 50 patients (86%) achieved an objective response, 33 patients (57%) achieved a complete remission (CR), and 17 patients (29%) achieved a partial remission. The median durations of overall response and CR were 12.6 and 13.2 months, respectively. Grade 3 or 4 adverse events in ? 10% of patients were neutropenia (21%), thrombocytopenia (14%), and peripheral sensory neuropathy (12%).Brentuximab vedotin induced objective responses in the majority of patients and CRs in more than half of patients with recurrent systemic ALCL. Targeted therapy with this CD30-directed antibody-drug conjugate may be an effective treatment for relapsed or refractory systemic ALCL and warrants further studies in front-line therapy.

    View details for DOI 10.1200/JCO.2011.38.0402

    View details for Web of Science ID 000305413200010

    View details for PubMedID 22614995

  • Cardiac toxicity associated with bevacizumab (Avastin) in combination with CHOP chemotherapy for peripheral T cell lymphoma in ECOG 2404 trial LEUKEMIA & LYMPHOMA Advani, R. H., Hong, F., Horning, S. J., Kahl, B. S., Manola, J., Swinnen, L. J., Habermann, T. M., Ganjoo, K. 2012; 53 (4): 718-720

    View details for DOI 10.3109/10428194.2011.623256

    View details for Web of Science ID 000302067100030

    View details for PubMedID 21916830

  • STAGE I-IIIA NON-BULKY HODGKIN'S LYMPHOMA. IS FURTHER DISTINCTION BASED ON PROGNOSTIC FACTORS USEFUL? THE STANFORD EXPERIENCE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Advani, R. H., Hoppe, R. T., Maeda, L. S., Baer, D. M., Mason, J., Rosenberg, S. A., Horning, S. J. 2011; 81 (5): 1374-1379

    Abstract

    In the United States, early-stage Hodgkin's lymphoma (HL) is defined as asymptomatic stage I/II non-bulky disease. European groups stratify patients to more intense treatment by considering additional unfavorable factors, such as age, number of nodal sites, sedimentation rate, extranodal disease, and elements of the international prognostic score for advanced HL. We sought to determine the prognostic significance of these factors in patients with early-stage disease treated at Stanford University Medical Center.This study was a retrospective analysis of 101 patients treated with abbreviated Stanford V chemotherapy (8 weeks) and 30-Gy (n=84 patients) or 20-Gy (n=17 patients) radiotherapy to involved sites. Outcomes were assessed after applying European risk factors.At a median follow-up of 8.5 years, freedom from progression (FFP) and overall survival (OS) rates were 94% and 97%, respectively. From 33% to 60% of our patients were unfavorable per European criteria (i.e., German Hodgkin Study Group [GHSG], n=55%; European Organization for Research and Treatment of Cancer, n=33%; and Groupe d'Etudes des Lymphomes de l'Adulte, n=61%). Differences in FFP rates between favorable and unfavorable patients were significant only for GHSG criteria (p=0.02) with there were no differences in OS rates for any criteria. Five of 6 patients who relapsed were successfully salvaged.The majority of our patients deemed unfavorable had an excellent outcome despite undergoing a significantly abbreviated regimen. Application of factors used by the GHSG defined a less favorable subset for FFP but with no impact on OS. As therapy for early-stage disease moves to further reductions in therapy, these factors take on added importance in the interpretation of current trial results and design of future studies.

    View details for DOI 10.1016/j.ijrobp.2010.07.041

    View details for Web of Science ID 000297602400024

    View details for PubMedID 20934280

  • MicroRNAs Are Independent Predictors of Outcome in Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP CLINICAL CANCER RESEARCH Alencar, A. J., Malumbres, R., Kozloski, G. A., Advani, R., Talreja, N., Chinichian, S., Briones, J., Natkunam, Y., Sehn, L. H., Gascoyne, R. D., Tibshirani, R., Lossos, I. S. 2011; 17 (12): 4125-4135

    Abstract

    Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power.We studied expression of 11 microRNAs (miRNA) that had previously been reported to have variable expression in DLBCL tumors. We measured the expression of each miRNA by quantitative real-time PCR analyses in 176 samples from uniformly treated DLBCL patients and correlated the results to survival.In a univariate analysis, the expression of miR-18a correlated with overall survival (OS), whereas the expression of miR-181a and miR-222 correlated with progression-free survival (PFS). A multivariate Cox regression analysis including the IPI, the 6-gene model-derived mortality predictor score and expression of the miR-18a, miR-181a, and miR-222, revealed that all variables were independent predictors of survival except the expression of miR-222 for OS and the expression of miR-18a for PFS.The expression of specific miRNAs may be useful for DLBCL survival prediction and their role in the pathogenesis of this disease should be examined further.

    View details for DOI 10.1158/1078-0432.CCR-11-0224

    View details for Web of Science ID 000291644700029

    View details for PubMedID 21525173

  • Current concepts and controversies in the management of early stage Hodgkin lymphoma LEUKEMIA & LYMPHOMA Maeda, L. S., Lee, M., Advani, R. H. 2011; 52 (6): 962-971

    Abstract

    Over the past three decades, due to the recognition of late effects related to high-dose extended field radiotherapy and heavy alkylator chemotherapy, combined modality therapy with abbreviated chemotherapy and limited field radiotherapy has emerged as the standard of care for early stage Hodgkin lymphoma, with cure rates in excess of 80%. Currently, however, controversy remains over identifying the most appropriate criteria to risk-stratify patients with early stage disease, so that those with a favorable prognosis receive limited treatment without compromising cure rates and those with unfavorable risk receive more intensified therapy. The optimal risk stratification system remains unclear, with variable definitions of favorable and unfavorable disease used by research groups in North America and Europe. Thus, comparison of clinical trial results has been challenging, and additional controversies persist regarding optimal chemotherapy regimens, duration of therapy, and the role of radiotherapy. Investigations are ongoing to assess the potential of functional imaging and biomarkers as tools for risk stratification. The collective goal is to further refine current stratification strategies to allow for an individualized, risk-adapted treatment approach that minimizes long-term late effects without compromising high cure rates.

    View details for DOI 10.3109/10428194.2011.557455

    View details for Web of Science ID 000290869100010

    View details for PubMedID 21463118

  • Optimal therapy of advanced Hodgkin lymphoma. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program Advani, R. 2011; 2011: 310-316

    Abstract

    Advanced-stage Hodgkin lymphoma (HL) has become a curable disease in the majority of patients. Research during the last decade has challenged chemotherapy with Adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) as the standard of care and debates continue regarding the role of radiation therapy (RT) in this patient population. The incorporation of interim positron emission tomography (PET) imaging and, recently, further characterization of HL on cellular and molecular levels are emerging as tools for treatment stratification and predictors of disease status. Newer targeted therapies have emerged that are very effective in the relapsed setting and are actively being explored as frontline therapy. Lastly, the expanding population of survivors cured of HL outnumbers patients with the disease and needs to be monitored for therapy-related late effects.

    View details for DOI 10.1182/asheducation-2011.1.310

    View details for PubMedID 22160051

  • Risk stratification in extranodal natural killer/T-cell lymphoma EXPERT REVIEW OF ANTICANCER THERAPY Kohrt, H., Lee, M., Advani, R. 2010; 10 (9): 1395-1405

    Abstract

    Extranodal natural killer/T-cell lymphoma (ENKL), a subtype of natural killer/T-cell malignancies, is a rare subset of lymphomas with significant biological and clinical heterogeneity. The prognosis of ENKL is variable and therapeutic approaches are not well established. The optimal dose, combination, and sequence of radiotherapy and chemotherapy are evolving, as is the role of stem cell transplantation. Radiotherapy is an essential component of therapy for early-stage disease. The clinical course of advanced disease is highly aggressive, with frequent chemotherapy resistance and a poor prognosis. For relapsed disease, asparaginase-based regimens have provided encouraging results and are currently under investigation in the frontline setting. Our article discusses the key aspects of biology, pathogenesis and clinical presentation that contribute to the heterogeneity, and proposes a stratified approach to the treatment of ENKL based on clinical, pathologic and biologic risk factors. Although considerable advances have been made in our understanding of the biology and prognosis of this lymphoma, it remains critical that all patients with a diagnosis of ENKL are enrolled and treated in clinical trials so that optimal therapies can be identified.

    View details for DOI 10.1586/ERA.10.130

    View details for Web of Science ID 000282259800012

    View details for PubMedID 20836675

  • Management of T-cell and natural-killer-cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009 LANCET ONCOLOGY Kwong, Y., Anderson, B. O., Advani, R., Kim, W., Levine, A. M., Lim, S. 2009; 10 (11): 1093-1101

    Abstract

    T-cell and natural-killer (NK)-cell lymphomas are neoplasms with geographical variations in frequencies. T-cell lymphomas are more prevalent in Asia than in Europe and North America, and NK-cell lymphomas occur almost exclusively in Asia and South America. These low frequencies mean that the diagnosis and optimum treatment of patients with T-cell and NK-cell lymphomas have not been studied prospectively in randomised controlled trials. Because T-cell and NK-cell lymphomas are more prevalent in Asia, the establishment of management recommendations by Asian oncologists in collaboration with international experts is pertinent. This review outlines guidelines commensurate with different levels of health-care resources and expertise. Consensus statements were formulated for diagnosis, staging, follow-up, and treatment approaches in patients with T-cell and NK-cell lymphomas--aimed at unifying the design of studies and interpretation of results. For patients not in clinical trials, consensus opinions offer useful guidelines on optimum management.

    View details for Web of Science ID 000271852800019

    View details for PubMedID 19880063

  • Phase I Study of the Humanized Anti-CD40 Monoclonal Antibody Dacetuzumab in Refractory or Recurrent Non-Hodgkin's Lymphoma JOURNAL OF CLINICAL ONCOLOGY Advani, R., Forero-Torres, A., Furman, R. R., Rosenblatt, J. D., Younes, A., Ren, H., Harrop, K., Whiting, N., Drachman, J. G. 2009; 27 (26): 4371-4377

    Abstract

    To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics, and antitumor activity of dacetuzumab in patients with refractory or recurrent B-cell non-Hodgkin's lymphoma (NHL).In this open-label, dose-escalation phase I study, dacetuzumab was administered to six cohorts of adult patients. In the first cohort, patients received 2 mg/kg weekly for 4 weeks; in all other cohorts, an intrapatient dose-escalation schedule was used with increasing doses up to a maximum of 8 mg/kg. Patients with clinical benefit after one cycle of dacetuzumab were eligible for a second cycle.In the 50 patients who received dacetuzumab, no dose dependence of adverse events (AEs) was observed. The most common AEs in >or= 20% of patients were fatigue, pyrexia, and headache; most were grade 1 or 2. Noninfectious inflammatory eye disorders occurred in 12% of patients. AEs grade >or= 3 occurred in 30% of patients and included disease progression, anemia, pleural effusion, and thrombocytopenia. Most laboratory abnormalities were grade 1 or 2; transient elevated hepatic aminotransferases occurred in 52% of patients. Two patients experienced dose-limiting toxicity: grade 3 conjunctivitis and transient vision loss in cohort (1), and grade 3 ALT elevation in cohort IV. The MTD of dacetuzumab was not established at the dose levels tested. Six objective responses were reported (one complete response, five partial responses). Tumor size decreased in approximately one third of patients.Dacetuzumab monotherapy was well tolerated in patients with NHL in doses up to 8 mg/kg/wk. Preliminary response data are encouraging and support additional studies of dacetuzumab in this patient population.

    View details for DOI 10.1200/JCO.2008.21.3017

    View details for Web of Science ID 000269652200024

    View details for PubMedID 19636010

  • Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Advani, R., Maeda, L., Lavori, P., Quon, A., Hoppe, R., Breslin, S., Rosenberg, S. A., Horning, S. J. 2007; 25 (25): 3902-3907

    Abstract

    To correlate [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) status after chemotherapy, but before radiation, with outcome in patients treated with the Stanford V regimen.We analyzed retrospectively 81 patients with Hodgkin's disease who had serial [(18)F]FDG-PET scans performed at baseline and again at the completion of Stanford V chemotherapy, before planned radiotherapy. Patients with favorable stage I/II (nonbulky mediastinal disease) and those with bulky mediastinal disease or stage III/IV were scanned after 8 and 12 weeks of chemotherapy, respectively. Radiotherapy fields were determined before starting chemotherapy based on baseline computed tomography scans.After chemotherapy, six of 81 patients had residual [(18)F]FDG-PET-positive sites, all in sites for which radiotherapy was planned. Four of the six patients with positive [(18)F]FDG-PET scans after chemotherapy experienced relapse compared with just three of 75 patients with negative [(18)F]FDG-PET scans. At a median follow-up of 4 years, the freedom from progression (FFP) was 96% in postchemotherapy [(18)F]FDG-PET-negative patients versus 33% in [(18)F]FDG-PET-positive patients (P < .0003). In a bivariate Cox model, [(18)F]FDG-PET positivity after chemotherapy remained a highly significant predictor of progression-free survival even after controlling for bulky disease and International Prognostic Score more than 2.These data indicate that PET status after chemotherapy is strongly predictive of FFP with the Stanford V regimen despite the use of consolidative radiotherapy. These results have implications for the design of clinical trials adapted to functional imaging.

    View details for DOI 10.1200/JCO.2007.11.9867

    View details for Web of Science ID 000249416000019

    View details for PubMedID 17664458

  • Angioimmunoblastic T cell lymphoma: Treatment experience with cyclosporine LEUKEMIA & LYMPHOMA Advani, R., Horwitz, S., Zelenetz, A., Horning, S. J. 2007; 48 (3): 521-525

    Abstract

    Angioimmunoblastic T cell lymphoma is a distinct entity for which there is no standard therapy. On the basis of the rationale that CsA may represent a novel drug for AITL, a disease with considerable immune dysregulation, and encouraging case reports, the authors have treated 12 patients with this agent. Ten had failed prior steroids and/or chemotherapy and two had no prior therapy. CsA was administered at a dose of 3 - 5 mg/kg PO bid for 6 - 8 weeks and gradually tapered by 50 mg every 1 - 3 weeks. Responding patients received a maintenance dose of 50 - 100 mg, with a gradual taper after a maximal response was achieved as tolerated. Doses were titrated for renal dysfunction or hypertension. CsA levels were not monitored. Eight of 12 patients responded (three complete and five partial remissions). Dose reductions were required in six patients; renal insufficiency (n = 3), fatigue (n = 2), and hypertension (n = 1). Two patients developed acute infections and one patient died shortly after active treatment. These results suggest that CsA deserves further testing as a novel therapy for AITL. By interrupting T-cell activation, CsA may alter the immune dysregulation that characterizes AILT. The efficacy of CsA is being explored in patients with recurrent AILT in a prospective trial (ECOG 2402).

    View details for DOI 10.1080/10428190601137658

    View details for Web of Science ID 000245108100015

    View details for PubMedID 17454592

  • Stage I and II follicular non-Hodgkin's lymphoma: Long-term follow-up of no initial therapy JOURNAL OF CLINICAL ONCOLOGY Advani, R., Rosenberg, S. A., Horning, S. J. 2004; 22 (8): 1454-1459

    Abstract

    To analyze the outcome of no initial therapy in stage I and II follicular small-cleaved (FSC) and follicular mixed (FM) non-Hodgkin's lymphoma (NHL) on overall survival, time to treatment, incidence and course of transformation, and cause of death.This was a retrospective analysis. Criteria for selection were patients with stage I and IIA FSC and FM (grades 1 and 2) NHL with therapy deferred for at least 3 months after diagnosis and a minimum follow-up of 1 year.Forty-three patients were identified (11 stage I, 32 stage II), with a median age of 58 years. Reasons for no initial therapy included: physician choice (n = 20), large abdominal radiation field required (n = 10), advanced age (n = 7), concern for xerostomia (n = 4), or patient refusal (n = 2). At a median follow-up of 86 months, 27 patients (63%) had not been treated. The median time to treatment in the remaining 16 patients was 22 months. Four of 16 patients transformed to a higher-grade lymphoma. Nine patients died-six due to progressive lymphoma. Estimated survivals at 5, 10, and 20 years were 97%, 85%, and 22%, respectively.In selected stage I and II follicular NHL patients, deferred therapy is an acceptable approach, as more than half of our patients remained untreated at a median of 6 or more years, and survival was comparable to that seen in reports with immediate treatment.

    View details for DOI 10.1200/JCO.2004.10.086

    View details for Web of Science ID 000220912200016

    View details for PubMedID 15024027

  • ACR APPROPRIATENESS CRITERIA (R) Localized Nodal Indolent Lymphoma ONCOLOGY-NEW YORK Hoppe, B. S., Hodgson, D. C., Advani, R., Dabaja, B. S., Flowers, C. R., Ha, C. S., Metzger, M. L., Plastaras, J. P., Roberts, K. B., Shapiro, R., Terezakis, S. A., Winkfield, K. M., Younes, A., Constine, L. S. 2013; 27 (8): 786-794
  • A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study LEUKEMIA & LYMPHOMA Foss, F. M., Sjak-Shie, N., Goy, A., Jacobsen, E., Advani, R., Smith, M. R., Komrokji, R., Pendergrass, K., Bolejack, V. 2013; 54 (7): 1373-1379

    Abstract

    This phase II study to determine the safety and efficacy of denileukin diftitox (DD) and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) enrolled patients with newly diagnosed peripheral T-cell lymphoma (PTCL). Forty-nine received DD 18 ?g/kg/day (days 1, 2) with CHOP (day 3) every 21 days for ? 6-8 cycles. Intent-to-treat (ITT) and safety populations comprised all patients. In the ITT population, the overall response rate was 65%, median duration of response was 30 months and median progression-free survival was 12 months. Median overall survival was not attained at the end of the study, and the overall survival rate was 63.3%. The two most frequent treatment-related adverse events (AEs) were fatigue and nausea. Most frequent AEs ? grade 3 within the hematologic system were lymphopenia (24.5%), neutropenia (20.4%) and leukopenia (18.4%). Three treatment-related deaths occurred. DD plus CHOP was well tolerated, and progression-free and overall survival improved versus historical comparison with CHOP alone. Confirmation in larger trials is warranted.

    View details for DOI 10.3109/10428194.2012.742521

    View details for Web of Science ID 000320698300009

    View details for PubMedID 23278639

  • Non-Hodgkin's Lymphomas, Version 1.2013 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M. A., Naganuma, M. 2013; 11 (3): 257-273
  • Non-Hodgkin's lymphomas, version 1.2013. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Dwyer, M. A., Naganuma, M. 2013; 11 (3): 257-272

    Abstract

    These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Non-Hodgkin's Lymphomas (NHL) and provide a discussion of the clinical evidence that support the updates. The updates discussed in this article feature recommendations for additional treatment options in patients with chronic lymphocytic leukemia and guidance surrounding the management of hepatitis virus reactivation/infections in high-risk patients with NHL undergoing antitumor therapy.

    View details for PubMedID 23486452

  • Gene Expression-Based Model Using Formalin-Fixed Paraffin-Embedded Biopsies Predicts Overall Survival in Advanced-Stage Classical Hodgkin Lymphoma JOURNAL OF CLINICAL ONCOLOGY Scott, D. W., Chan, F. C., Hong, F., Rogic, S., Tan, K. L., Meissner, B., Ben-Neriah, S., Boyle, M., Kridel, R., Telenius, A., Woolcock, B. W., Farinha, P., Fisher, R. I., Rimsza, L. M., Bartlett, N. L., Cheson, B. D., Shepherd, L. E., Advani, R. H., Connors, J. M., Kahl, B. S., Gordon, L. I., Horning, S. J., Steidl, C., Gascoyne, R. D. 2013; 31 (6): 692-700

    Abstract

    Our aim was to reliably identify patients with advanced-stage classical Hodgkin lymphoma (cHL) at increased risk of death by developing a robust predictor of overall survival (OS) using gene expression measured in routinely available formalin-fixed paraffin-embedded tissue (FFPET).Expression levels of 259 genes, including those previously reported to be associated with outcome in cHL, were determined by digital expression profiling of pretreatment FFPET biopsies from 290 patients enrolled onto the E2496 Intergroup trial comparing doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and Stanford V regimens in locally extensive and advanced-stage cHL. A model for OS separating patients into low- and high-risk groups was produced using penalized Cox regression. The model was tested in an independent cohort of 78 patients enriched for treatment failure but otherwise similar to patients in a population-based registry of patients treated with ABVD. Weighted analysis methods generated unbiased estimates of predictor performance in the population-based registry.A 23-gene outcome predictor was generated. The model identified a population at increased risk of death in the validation cohort. There was a 29% absolute difference in 5-year OS between the high- and low-risk groups (63% v 92%, respectively; log-rank P < .001; hazard ratio, 6.7; 95% CI, 2.6 to 17.4). The predictor was superior to the International Prognostic Score and CD68 immunohistochemistry in multivariate analyses.A gene expression-based predictor, developed in and applicable to routinely available FFPET biopsies, identifies patients with advanced-stage cHL at increased risk of death when treated with standard-intensity up-front regimens.

    View details for DOI 10.1200/JCO.2012.43.4589

    View details for Web of Science ID 000315086400017

    View details for PubMedID 23182984

  • Non-Hodgkin's Lymphomas, version 3.2012. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Naganuma, M., Dwyer, M. A. 2012; 10 (12): 1487-1498

    Abstract

    These NCCN Guidelines Insights summarize several key updates to the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas (NHL) and describe the clinical evidence supporting the updates. The featured updates include changes to the recommendations for treatment options in patients with chronic lymphocytic leukemia (including in elderly or frail patients and patients with poor-risk cytogenetics), guidance surrounding surveillance imaging for follow-up of patients with NHL, and the addition of first-line consolidation options for patients with mantle cell lymphoma.

    View details for PubMedID 23221787

  • Non-Hodgkin's Lymphomas, Version 3.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Wierda, W. G., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., Krivacic, S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L., Tsien, C., Vose, J. M., Yahalom, J., Zafar, N., Naganuma, M., Dwyer, M. A. 2012; 10 (12): 1487-1498
  • Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines PLOS ONE Powell, A. A., Talasaz, A. H., Zhang, H., Coram, M. A., Reddy, A., Deng, G., Telli, M. L., Advani, R. H., Carlson, R. W., Mollick, J. A., Sheth, S., Kurian, A. W., Ford, J. M., Stockdale, F. E., Quake, S. R., Pease, R. F., Mindrinos, M. N., Bhanot, G., Dairkee, S. H., Davis, R. W., Jeffrey, S. S. 2012; 7 (5)

    Abstract

    To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery.We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy.For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery.

    View details for DOI 10.1371/journal.pone.0033788

    View details for Web of Science ID 000305335000005

    View details for PubMedID 22586443

  • Hodgkin Lymphoma, Version 2.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Aoun, P., Bello, C. M., Bierman, P. J., Blum, K. A., Chen, R., Dabaja, B., Duron, Y., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Maloney, D. G., Mansur, D., Mauch, P. M., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Poppe, M., Pro, B., Winter, J. N., Yahalom, J., Sundar, H. 2012; 10 (5): 589-597

    Abstract

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin Lymphoma (HL) include the clinical management of classical HL and lymphocyte-predominant HL (LPHL). Major changes have been incorporated into these guidelines since their inception. In the 2012 NCCN Guidelines for HL, PET scans are not recommended for interim restaging of patients with stage I to II favorable disease. After reevaluating the available evidence on the use of interim PET imaging, the panel recommends the use of diagnostic CT scan of involved sites for interim restaging after completion of chemotherapy for this group of patients. Maintenance rituximab for 2 years is included as an option for patients with stage IB to IIB or stage III to IV LPHL treated with rituximab alone in the first-line setting. Brentuximab vedotin is included as an option for patients with progressive disease or relapsed disease after second-line chemotherapy or high-dose therapy with autologous stem cell rescue.

    View details for Web of Science ID 000303557700005

    View details for PubMedID 22570290

  • Interim-treatment quantitative PET parameters predict progression and death among patients with hodgkin's disease RADIATION ONCOLOGY Tseng, D., Rachakonda, L. P., Su, Z., Advani, R., Horning, S., Hoppe, R. T., Quon, A., Graves, E. E., Loo, B. W., Tran, P. T. 2012; 7

    Abstract

    We hypothesized that quantitative PET parameters may have predictive value beyond that of traditional clinical factors such as the International Prognostic Score (IPS) among Hodgkin's disease (HD) patients.Thirty HD patients treated at presentation or relapse had staging and interim-treatment PET-CT scans. The majority of patients (53%) had stage III-IV disease and 67% had IPS ? 2. Interim-treatment scans were performed at a median of 55 days from the staging PET-CT. Chemotherapy regimens used: Stanford V (67%), ABVD (17%), VAMP (10%), or BEACOPP (7%). Hypermetabolic tumor regions were segmented semiautomatically and the metabolic tumor volume (MTV), mean standardized uptake value (SUV mean), maximum SUV (SUV max) and integrated SUV (iSUV) were recorded. We analyzed whether IPS, absolute value PET parameters or the calculated ratio of interim- to pre-treatment PET parameters were associated with progression free survival (PFS) or overall survival (OS).Median follow-up of the study group was 50 months. Six of the 30 patients progressed clinically. Absolute value PET parameters from pre-treatment scans were not significant. Absolute value SUV max from interim-treatment scans was associated with OS as determined by univariate analysis (p < 0.01). All four calculated PET parameters (interim/pre-treatment values) were associated with OS: MTV int/pre (p < 0.01), SUV mean int/pre (p < 0.05), SUV max int/pre (p = 0.01), and iSUV int/pre (p < 0.01). Absolute value SUV max from interim-treatment scans was associated with PFS (p = 0.01). Three calculated PET parameters (int/pre-treatment values) were associated with PFS: MTV int/pre (p = 0.01), SUV max int/pre (p = 0.02) and iSUV int/pre (p = 0.01). IPS was associated with PFS (p < 0.05) and OS (p < 0.01).Calculated PET metrics may provide predictive information beyond that of traditional clinical factors and may identify patients at high risk of treatment failure early for treatment intensification.

    View details for DOI 10.1186/1748-717X-7-5

    View details for Web of Science ID 000301710700001

    View details for PubMedID 22260710

  • In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study BLOOD Kim, Y. H., Gratzinger, D., Harrison, C., Brody, J. D., Czerwinski, D. K., Ai, W. Z., Morales, A., Abdulla, F., Xing, L., Navi, D., Tibshirani, R. J., Advani, R. H., Lingala, B., Shah, S., Hoppe, R. T., Levy, R. 2012; 119 (2): 355-363

    Abstract

    We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8(+) T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25(+), Foxp3(+) T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100(+), CD1a(+) dendritic cells. There was a trend toward greater reduction of CD25(+) T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.

    View details for DOI 10.1182/blood-2011-05-355222

    View details for Web of Science ID 000299268900012

    View details for PubMedID 22045986

  • A Phase I Weekly Dosing Study of Brentuximab Vedotin in Patients with Relapsed/Refractory CD30-Positive Hematologic Malignancies CLINICAL CANCER RESEARCH Fanale, M. A., Forero-Torres, A., Rosenblatt, J. D., Advani, R. H., Franklin, A. R., Kennedy, D. A., Han, T. H., Sievers, E. L., Bartlett, N. L. 2012; 18 (1): 248-255

    Abstract

    The antibody-drug conjugate (ADC) brentuximab vedotin comprises a CD30-directed antibody covalently attached to the potent antimicrotubule agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. This study explored the safety, maximum-tolerated dose (MTD), and activity of weekly dosing of brentuximab vedotin in patients with relapsed or refractory CD30-positive hematologic malignancies.In this phase I dose-escalation study, brentuximab vedotin was administered intravenously on Days 1, 8, and 15, of each 28-day cycle at doses ranging from 0.4 to 1.4 mg/kg. Forty-four patients were enrolled: 38 with Hodgkin lymphoma, five with systemic anaplastic large cell lymphoma, and one with peripheral T-cell lymphoma not otherwise specified. Doses were escalated in increments of 0.2 mg/kg until dose-limiting toxicity (DLT) was observed. Patients were monitored for antitherapeutic antibodies and pharmacokinetic parameters. Antitumor assessments were carried out every two cycles.The MTD was 1.2 mg/kg. The most common adverse events were peripheral sensory neuropathy, fatigue, nausea, diarrhea, arthralgia, and pyrexia; and the majority of events were mild to moderate in severity. Tumor regression occurred in 85% of patients and the overall objective response rate was 59% (n = 24), with 34% (n = 14) complete remissions. The median duration of response was not reached at a median follow-up of 45 weeks on study.Weekly administration of brentuximab vedotin resulted in tumor regression and durable remissions in patients with CD30-positive malignancies. This ADC was associated with manageable toxicity, including peripheral neuropathy. Further study in CD30-positive malignancies is warranted.

    View details for DOI 10.1158/1078-0432.CCR-11-1425

    View details for Web of Science ID 000298758900026

    View details for PubMedID 22080439

  • Phase I trial of oblimersen (GenasenseA (R)) and gemcitabine in refractory and advanced malignancies INVESTIGATIONAL NEW DRUGS Galatin, P. S., Advani, R. H., Fisher, G. A., Francisco, B., Julian, T., Losa, R., Sierra, M. I., Sikic, B. I. 2011; 29 (5): 971-977

    Abstract

    Overexpression of Bcl-2 is associated with worse prognosis for a number of cancer types. The present study was designed to determine the maximum tolerated dose (MTD) of oblimersen (antisense Bcl-2) and gemcitabine when administered to patients with refractory malignancies.Sixteen patients with advanced solid tumors refractory to standard therapies were treated with escalating doses of oblimersen continuous, 120-h intravenous infusion given every 14 days, with a fixed-dose-rate intravenous infusion of gemcitabine administered on day 5 of each cycle. Serial plasma samples were collected to calculate the pharmacokinetics of oblimersen and gemcitabine, and also to measure the effect of oblimersen on Bcl-2 expression.7 women and 9 men, median age 55 years (range 35-74 years), received a 5-day infusion of oblimersen at dose levels of 5 mg/kg/day (n = 4) or 7 mg/kg/day (n = 12). On the 5th day of the infusion, gemcitabine was given at 10 mg/m(2)/h for a total dose of 1,000 mg/m(2) (n = 7; cohorts I and II), 1,200 mg/m(2) (n = 3; cohort III), or 1,500 mg/m(2) (n = 6; cohort IV). Edema was the dose-limiting toxicity (DLT), necessitating expansion of cohort IV. No subsequent DLTs were noted. Thus, the maximum planned doses were well tolerated, and a formal MTD was not determined. Most hematologic toxicities were grade 1 or 2. There was low-grade fatigue, nausea/vomiting, and myalgias/arthralgias. Oblimersen C(ss) and AUC increased in relation to the dose escalation, but gemcitabine triphosphate levels did not correlate well with dose. There were no objective responses, though 5 patients had stable disease. A >75% reduction in Bcl-2 expression in peripheral blood mononuclear leucocytes was seen more frequently in patients who achieved stable disease than in progressing patients.The maximal planned dose levels of oblimersen and gemcitabine in combination were well tolerated. Only one DLT (edema) occurred. There was a correlation between Bcl-2 reduction and stable disease. The recommended doses of the drugs for future studies are 7 mg/kg/day of oblimersen on days 1-5, and gemcitabine 1,500 mg/m(2) on day 5, every two weeks.

    View details for DOI 10.1007/s10637-010-9416-4

    View details for Web of Science ID 000294223500027

    View details for PubMedID 20349264

  • Hodgkin lymphoma. Journal of the National Comprehensive Cancer Network Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Bello, C. M., Bierman, P. J., Blum, K. A., Dabaja, B., Duron, Y., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Maloney, D. G., Mansur, D., Mauch, P. M., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Poppe, M., Pro, B., Weiss, L., Winter, J. N., Yahalom, J. 2011; 9 (9): 1020-1058

    View details for PubMedID 21917626

  • NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hoppe, R. T., Advani, R. H., Ai, W. Z., Ambinder, R. F., Bello, C. M., Bierman, P. J., Blum, K. A., Dabaja, B., Duron, Y., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hochberg, E. P., Maloney, D. G., Mansur, D., Mauch, P. M., Metzger, M., Moore, J. O., Morgan, D., Moskowitz, C. H., Poppe, M., Pro, B., Weiss, L., Winter, J. N., Yahalom, J. 2011; 9 (9): 1020-1058
  • Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment BLOOD Alizadeh, A. A., Gentles, A. J., Alencar, A. J., Liu, C. L., Kohrt, H. E., Houot, R., Goldstein, M. J., Zhao, S., Natkunam, Y., Advani, R. H., Gascoyne, R. D., Briones, J., Tibshirani, R. J., Myklebust, J. H., Plevritis, S. K., Lossos, I. S., Levy, R. 2011; 118 (5): 1350-1358

    Abstract

    Several gene-expression signatures predict survival in diffuse large B-cell lymphoma (DLBCL), but the lack of practical methods for genome-scale analysis has limited translation to clinical practice. We built and validated a simple model using one gene expressed by tumor cells and another expressed by host immune cells, assessing added prognostic value to the clinical International Prognostic Index (IPI). LIM domain only 2 (LMO2) was validated as an independent predictor of survival and the "germinal center B cell-like" subtype. Expression of tumor necrosis factor receptor superfamily member 9 (TNFRSF9) from the DLBCL microenvironment was the best gene in bivariate combination with LMO2. Study of TNFRSF9 tissue expression in 95 patients with DLBCL showed expression limited to infiltrating T cells. A model integrating these 2 genes was independent of "cell-of-origin" classification, "stromal signatures," IPI, and added to the predictive power of the IPI. A composite score integrating these genes with IPI performed well in 3 independent cohorts of 545 DLBCL patients, as well as in a simple assay of routine formalin-fixed specimens from a new validation cohort of 147 patients with DLBCL. We conclude that the measurement of a single gene expressed by tumor cells (LMO2) and a single gene expressed by the immune microenvironment (TNFRSF9) powerfully predicts overall survival in patients with DLBCL.

    View details for DOI 10.1182/blood-2011-03-345272

    View details for Web of Science ID 000293510000028

    View details for PubMedID 21670469

  • Lymphoma in Pregnancy Initially Diagnosed as Vaginal Intraepithelial Neoplasia and Lichen Planus OBSTETRICS AND GYNECOLOGY Thuong-Thuong Nguyen, T. T., Gubens, M., Arber, D. A., Advani, R., Juretzka, M., Aziz, N. 2011; 118 (2): 486-489

    Abstract

    Non-Hodgkin's lymphoma presenting as a vaginal mass in pregnancy is uncommon.A 38-year-old primigravid woman presented at 27 weeks of gestation with vaginal lesions, bleeding, and discharge. Previous vaginal biopsies had been consistent with vaginal intraepithelial neoplasia 1 and lichen planus. After admission for this enlarging vaginal mass and bleeding, she was noted to have a newly palpable breast mass. Biopsy of the breast mass and subsequent re-evaluation of original vaginal biopsies were consistent with diffuse large B-cell lymphoma. She was treated with chemoimmunotherapy during pregnancy and delivered a viable neonate at term.Although benign vaginal conditions are common, non-Hodgkin's lymphoma should be considered in the differential diagnosis of persistent or enlarging vaginal lesions in pregnancy.

    View details for DOI 10.1097/AOG.0b013e3182234d12

    View details for Web of Science ID 000293115000027

    View details for PubMedID 21768862

  • Non-Hodgkin's Lymphomas JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Abramson, J. S., Advani, R. H., Andreadis, C. B., Bartlett, N., Bellam, N., Byrd, J. C., Czuczman, M. S., Fayad, L. E., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kelsey, C. R., Kim, Y. H., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Pro, B., Reddy, N., Sokol, L., Swinnen, L. J., Tsien, C., Vose, J. M., Wierda, W. G., Yahalom, J., Zafar, N. 2011; 9 (5): 484-560

    View details for Web of Science ID 000290292400005

    View details for PubMedID 21550968

  • ACR Appropriateness Criteria (R) on Hodgkin's Lymphoma-Unfavorable Clinical Stage I and II JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Das, P., Ng, A., Constine, L. S., Advani, R., Flowers, C., Friedberg, J., Hodgson, D. C., Schwartz, C. L., Wilder, R. B., Wilson, L. D., Yunes, M. J. 2011; 8 (5): 302-308

    Abstract

    Combined-modality therapy, consisting of chemotherapy followed by radiation therapy (RT), represents the standard of care for most patients with unfavorable-prognosis early-stage Hodgkin's lymphoma. The most widely accepted chemotherapy regimen is ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine); however, recent trials have evaluated other regimens such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and Stanford V. After chemotherapy, the standard radiation field is involved-field RT, although there is increasing interest now in involved-node RT. The authors review recent trials on chemotherapy and RT for unfavorable-prognosis early-stage Hodgkin's lymphoma. This article presents illustrative clinical cases, with treatment recommendations from an expert panel of radiation oncologists and medical oncologists.

    View details for DOI 10.1016/j.jacr.2011.01.009

    View details for Web of Science ID 000306201300006

    View details for PubMedID 21531305

  • CD40 Pathway Activation Status Predicts Response to CD40 Therapy in Diffuse Large B Cell Lymphoma SCIENCE TRANSLATIONAL MEDICINE Burington, B., Yue, P., Shi, X., Advani, R., Lau, J. T., Tan, J., Stinson, S., Stinson, J., Januario, T., de Vos, S., Ansell, S., Forero-Torres, A., Fedorowicz, G., Yang, T. T., Elkins, K., Du, C., Mohan, S., Yu, N., Modrusan, Z., Seshagiri, S., Yu, S., Pandita, A., Koeppen, H., French, D., Polson, A. G., Offringa, R., Whiting, N., Ebens, A., Dornan, D. 2011; 3 (74)

    Abstract

    The primary function of B cells, critical components of the adaptive immune response, is to produce antibodies against foreign antigens, as well as to perform isotype class switching, which changes the heavy chain of an antibody so that it can interact with different repertoires of effector cells. CD40 is a member of the tumor necrosis factor superfamily of cell surface receptors that transmits survival signals to B cells. In contrast, in B cell cancers, stimulation of CD40 signaling results in a heterogeneous response in which cells can sometimes undergo cell death in response to treatment, depending on the system studied. We found an association between sensitivity to CD40 stimulation and mutation of the tumor suppressor p53 in a panel of non-Hodgkin's lymphoma cell lines. Consistent with p53's tumor suppressor role, we found that higher levels of intrinsic DNA damage and increased proliferation rates, as well as higher levels of BCL6, a transcriptional repressor proto-oncogene, were associated with sensitivity to CD40 stimulation. In addition, CD40 treatment-resistant cell lines were sensitized to CD40 stimulation after the introduction of DNA-damaging agents. Using gene expression analysis, we also showed that resistant cell lines exhibited a preexisting activated CD40 pathway and that an mRNA expression signature comprising CD40 target genes predicted sensitivity and resistance to CD40-activating agents in cell lines and mouse xenograft models. Finally, the gene signature predicted tumor shrinkage and progression-free survival in patients with diffuse large B cell lymphoma treated with dacetuzumab, a monoclonal antibody with partial CD40 agonist activity. These data show that CD40 pathway activation status may be useful in predicting the antitumor activity of CD40-stimulating therapeutic drugs.

    View details for DOI 10.1126/scitranslmed.3001620

    View details for Web of Science ID 000292974200002

    View details for PubMedID 21411738

  • In Situ Vaccination With a TLR9 Agonist Induces Systemic Lymphoma Regression: A Phase I/II Study JOURNAL OF CLINICAL ONCOLOGY Brody, J. D., Ai, W. Z., Czerwinski, D. K., Torchia, J. A., Levy, M., Advani, R. H., Kim, Y. H., Hoppe, R. T., Knox, S. J., Shin, L. K., Wapnir, I., Tibshirani, R. J., Levy, R. 2010; 28 (28): 4324-4332

    Abstract

    Combining tumor antigens with an immunostimulant can induce the immune system to specifically eliminate cancer cells. Generally, this combination is accomplished in an ex vivo, customized manner. In a preclinical lymphoma model, intratumoral injection of a Toll-like receptor 9 (TLR9) agonist induced systemic antitumor immunity and cured large, disseminated tumors.We treated 15 patients with low-grade B-cell lymphoma using low-dose radiotherapy to a single tumor site and-at that same site-injected the C-G enriched, synthetic oligodeoxynucleotide (also referred to as CpG) TLR9 agonist PF-3512676. Clinical responses were assessed at distant, untreated tumor sites. Immune responses were evaluated by measuring T-cell activation after in vitro restimulation with autologous tumor cells.This in situ vaccination maneuver was well-tolerated with only grade 1 to 2 local or systemic reactions and no treatment-limiting adverse events. One patient had a complete clinical response, three others had partial responses, and two patients had stable but continually regressing disease for periods significantly longer than that achieved with prior therapies. Vaccination induced tumor-reactive memory CD8 T cells. Some patients' tumors were able to induce a suppressive, regulatory phenotype in autologous T cells in vitro; these patients tended to have a shorter time to disease progression. One clinically responding patient received a second course of vaccination after relapse resulting in a second, more rapid clinical response.In situ tumor vaccination with a TLR9 agonist induces systemic antilymphoma clinical responses. This maneuver is clinically feasible and does not require the production of a customized vaccine product.

    View details for DOI 10.1200/JCO.2010.28.9793

    View details for Web of Science ID 000282272700032

    View details for PubMedID 20697067

  • Voreloxin, a First-in-Class Anticancer Quinolone Derivative, in Relapsed/Refractory Solid Tumors: A Report on Two Dosing Schedules CLINICAL CANCER RESEARCH Advani, R. H., Hurwitz, H. I., Gordon, M. S., Ebbinghaus, S. W., Mendelson, D. S., Wakelee, H. A., Hoch, U., Silverman, J. A., Havrilla, N. A., Berman, C. J., Fox, J. A., Allen, R. S., Adelman, D. C. 2010; 16 (7): 2167-2175

    Abstract

    Voreloxin, a novel replication-dependent DNA-damaging agent, intercalates DNA and inhibits topoisomerase II. Voreloxin induces site-selective DNA double-strand breaks and apoptosis. We report the phase 1 experience of voreloxin in patients with relapsed/refractory solid tumors, including dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), pharmacokinetics, and clinical activity.Two dose-escalation studies evaluated voreloxin administered i.v. every 3 weeks (SPO-0001) or weekly for 3 weeks every 28 days (SPO-0002). In SPO-0001, patients were classified as heavily pretreated (HP) or minimally pretreated (MP) based on therapeutic history.In the SPO-0001 study, 41 patients (24 HP/17 MP) were treated in eight dose cohorts (3-75 mg/m(2)). At 60 mg/m(2), four HP patients experienced DLTs: grade 4 neutropenia (n = 3, one with fever) and grade 3 febrile neutropenia/pneumonia (n = 1). At 75 mg/m(2), two MP patients experienced DLTs: grade 4 neutropenia/thrombocytopenia (n = 1) or grade 2 oral thrush for >29 days (n = 1). Therefore, the MTD was 48 mg/m(2) (HP patients) and 60 mg/m(2) (MP patients). In the SPO-0002 study, 21 patients were treated in six dose cohorts (3-24 mg/m(2)). At 18 mg/m(2), two patients experienced DLTs: grade 3 neutropenia, one with pleural effusion (>14 days each). The MTD was 15 mg/m(2). Voreloxin exhibited low clearance (2 L/h/m(2)), a long terminal half-life (22 hours), and dose-proportional exposure. Overall, 31 of 62 patients had stable disease and 1 patient (ovarian cancer) had a partial response per Rustin criteria.Voreloxin showed an acceptable safety profile with clinical activity in patients with relapsed/refractory solid tumors. The MTD was schedule-dependent. Voreloxin is currently in clinical studies of ovarian cancer and acute myeloid leukemia.

    View details for DOI 10.1158/1078-0432.CCR-09-2236

    View details for Web of Science ID 000278595800021

    View details for PubMedID 20233886

  • Non-Hodgkin's Lymphomas JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Zelenetz, A. D., Abramson, J. S., Advani, R. H., Andreadis, C. B., Byrd, J. C., Czuczman, M. S., Fayad, L., Forero, A., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kaminski, M. S., Kim, Y. H., LaCasce, A. S., Mughal, T. I., Nademanee, A., Porcu, P., Press, O., Prosnitz, L., Reddy, N., Smith, M. R., Sokol, L., Swinnen, L., Vose, J. M., Wierda, W. G., Yahalom, J., Yunus, F. 2010; 8 (3): 288-334
  • NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Abramson, J. S., Advani, R. H., Andreadis, C. B., Byrd, J. C., Czuczman, M. S., Fayad, L., Forero, A., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kaminski, M. S., Kim, Y. H., LaCasce, A. S., Mughal, T. I., Nademanee, A., Porcu, P., Press, O., Prosnitz, L., Reddy, N., Smith, M. R., Sokol, L., Swinnen, L., Vose, J. M., Wierda, W. G., Yahalom, J., Yunus, F. 2010; 8 (3): 288-334

    View details for PubMedID 20202462

  • Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study BLOOD Horning, S. J., Juweid, M. E., Schoeder, H., Wiseman, G., McMillan, A., Swinnen, L. J., Advani, R., Gascoyne, R., Quon, A. 2010; 115 (4): 775-777

    Abstract

    Positive interim positron emission tomography (PET) scans are thought to be associated with inferior outcomes in diffuse large B-cell lymphoma. In the E3404 diffuse large B-cell lymphoma study, PET scans at baseline and after 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone were centrally reviewed by a single reader. To determine the reproducibility of interim PET interpretation, an expert panel of 3 external nuclear medicine physicians visually scored baseline and interim PET scans independently and were blinded to clinical information. The binary Eastern Cooperative Oncology Group (ECOG) study criteria were based on modifications of the Harmonization Criteria; the London criteria were also applied. Of 38 interim scans, agreement was complete in 68% and 71% by ECOG and London criteria, respectively. The range of PET(+) interim scans was 16% to 34% (P = not significant) by reviewer. Moderate consistency of reviews was observed: kappa statistic = 0.445 using ECOG criteria, and kappa statistic = 0.502 using London criteria. These data, showing only moderate reproducibility among nuclear medicine experts, indicate the need to standardize PET interpretation in research and practice. This trial was registered at www.clinicaltrials.gov as #NCT00274924 [corrected].

    View details for DOI 10.1182/blood-2009-08-234351

    View details for Web of Science ID 000274086600008

    View details for PubMedID 19767508

  • Lymphoma cell VEGFR2 expression detected by immunohistochemistry predicts poor overall survival in diffuse large B cell lymphoma treated with immunochemotherapy (R-CHOP) BRITISH JOURNAL OF HAEMATOLOGY Gratzinger, D., Advani, R., Zhao, S., Talreja, N., Tibshirani, R. J., Shyam, R., Horning, S., Sehn, L. H., Farinha, P., Briones, J., Lossos, I. S., Gascoyne, R. D., Natkunam, Y. 2010; 148 (2): 235-244

    Abstract

    Diffuse large B cell lymphoma (DLBCL) is clinically and biologically heterogeneous. In most cases of DLBCL, lymphoma cells co-express vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2, suggesting autocrine in addition to angiogenic effects. We enumerated microvessel density and scored lymphoma cell expression of VEGF, VEGFR1, VEGFR2 and phosphorylated VEGFR2 in 162 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone)-like regimens. VEGFR2 expression correlated with shorter overall survival (OS) independent of International Prognostic Index (IPI) (P = 0.0028). Phosphorylated VEGFR2 (detected in 13% of cases) correlated with shorter progression-free survival (PFS, P = 0.044) and trended toward shorter OS on univariate analysis. VEGFR1 was not predictive of survival on univariate analysis, but it did correlate with better OS on multivariate analysis with VEGF, VEGFR2 and IPI (P = 0.036); in patients with weak VEGFR2, lack of VEGFR1 coexpression was significantly correlated with poor OS independent of IPI (P = 0.01). These results are concordant with our prior finding of an association of VEGFR1 with longer OS in DLBCL treated with chemotherapy alone. We postulate that VEGFR1 may oppose autocrine VEGFR2 signalling in DLBCL by competing for VEGF binding. In contrast to our prior results with chemotherapy alone, microvessel density was not prognostic of PFS or OS with R-CHOP-like therapy.

    View details for DOI 10.1111/j.1365-2141.2009.07942.x

    View details for Web of Science ID 000272884100006

    View details for PubMedID 19821819

  • The emerging role for rituximab in the treatment of nodular lymphocyte predominant Hodgkin lymphoma CURRENT OPINION IN ONCOLOGY Maeda, L. S., Advani, R. H. 2009; 21 (5): 397-400

    Abstract

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subset of Hodgkin lymphoma that is distinct from classical Hodgkin lymphoma (cHL). The unique malignant 'popcorn' cells express the B-cell antigen CD20 and lack expression of the cHL markers CD15 and CD30. Traditionally, NLPHL has been included with cHL in clinical trials with excellent prognosis reported in several series. The reliable expression of CD20 has led to the evaluation of the chimeric monoclonal anti-CD20 antibody rituximab in several recent trials.Three series have reported the efficacy of 4 weekly doses of rituximab in all stages of NLPHL, both in the treatment-naive and relapsed settings. Emerging data also suggest that longer courses of antibody therapy may improve the duration of response.Rituximab appears to offer a nonchemotherapy-based effective treatment option, which is well tolerated. Ongoing studies are required to further define the optimal patient population who may benefit from rituximab and evaluate its role in maintenance as well as in combination with radiotherapy and chemotherapy.

    View details for DOI 10.1097/CCO.0b013e32832f3ca3

    View details for Web of Science ID 000269172400002

    View details for PubMedID 19606035

  • Prognostic Factors in Primary Cutaneous Anaplastic Large Cell Lymphoma Characterization of Clinical Subset With Worse Outcome ARCHIVES OF DERMATOLOGY Woo, D. K., Jones, C. R., Vanoli-Storz, M. N., Kohler, S., Reddy, S., Advani, R., Hoppe, R. T., Kim, Y. H. 2009; 145 (6): 667-674

    Abstract

    To identify prognostic factors in primary cutaneous anaplastic large cell lymphoma (pcALCL), focusing on extensive limb disease (ELD), defined as initial presentation or progression to multiple skin tumors in 1 limb or contiguous body regions, and to study gene expression profiles of patients with pcALCL.Retrospective cohort study.The Stanford Comprehensive Cancer Center and dermatology ambulatory clinics.A total of 48 patients with pcALCL evaluated from 1990 through 2005.Hazard ratios (HRs) for prognostic factors for overall survival (OS) and disease-specific survival (DSS) and risk factors for progression to extracutaneous disease were identified using Cox regression. Gene expression profiles of 9 typical pcALCL and 3 ELD samples were investigated using complementary DNA microarrays.Univariate analysis demonstrated age, ELD, and progression to extracutaneous disease as significant prognostic factors for OS, whereas ELD and progression to extracutaneous disease were significant for DSS. In multivariate analysis, age (HR, 1.83; 95% confidence interval [CI], 1.02-3.26) and progression to extracutaneous disease (HR, 6.42; 95% CI, 1.39-29.68) remained significant for OS, whereas ELD (HR, 29.31; 95% CI, 1.72-500.82) and progression to extracutaneous disease (HR, 13.12; 95% CI, 1.03-167.96) remained independent prognostic factors for DSS. Presentation with T3 disease was a risk factor for progression to extracutaneous disease (HR, 10.20; 95% CI, 1.84-56.72). Microarray data revealed that patients with ELD and typical pcALCL formed distinct clusters.Patients with ELD have a more aggressive course associated with a differential gene expression profile. More aggressive treatments may be indicated for patients with ELD and those whose disease progresses to extracutaneous disease because they have poorer outcomes.

    View details for Web of Science ID 000267010900006

    View details for PubMedID 19528422

  • Targeting CD40 in Waldenstrom's Macroglobulinemia CLINICAL LYMPHOMA & MYELOMA Lee, M., Advani, R. 2009; 9 (1): 87-89

    Abstract

    CD40 is a member of the tumor necrosis factor (TNF) receptor family and is expressed in a majority of B-cell malignancies. In Waldenström's macroglobulinemia (WM), CD40 expression is a common feature of bone marrow infiltrating lymphoplasmacytic cells, and preclinical evidence suggests that CD40 signaling is functionally important for WM growth and survival. Two antibodies targeting CD40 (SGN-40 and HCD 122 [Chir 12.12]) are currently undergoing clinical testing in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). HCD122 is a novel, fully human, IgG1 antagonistic monoclonal antibody while SGN-40 is a humanized IgG1 partial agonistic antibody. Both agents have demonstrated activity in preclinical models and are potent mediators of antibodydependent cellular cytotoxicity (ADCC). Clinically, phase I data suggest both agents are well tolerated with no immunogenicity and have early evidence of single-agent clinical activity in relapsed and refractory NHL and MM. These observations support the testing of CD40-targeted agents in WM.

    View details for DOI 10.3816/CLM.2009.n.023

    View details for Web of Science ID 000264628200023

    View details for PubMedID 19362983

  • Extranodal natural killer/T-cell lymphoma: current concepts in biology and treatment LEUKEMIA & LYMPHOMA Kohrt, H., Advani, R. 2009; 50 (11): 1773-1784

    Abstract

    Natural killer/T-cell (NK/T) lymphomas represent a group of rare tumors of NK and NK-T cells. The World Health Organization classifies NK-cell tumors into three types, extranodal NK/T-cell lymphomas (ENKL, nasal and non-nasal), NK-cell leukemias, and a blastic variant (CD4-positive, CD56-positive hematodermic neoplasms). We focus our review to the current concepts in biology and treatment of ENKL. Though considerable advances have been made in our understanding of NK-cell biology, malignant transformation including the role of Epstein-Barr virus, and prognosis, the rare nature of ENKL and its heterogeneity limit the ability to standardize therapy. Radiotherapy is fundamental to treatment of early-stage disease with a role for chemoradiotherapy among high-risk patients. The clinical course of advanced disease is highly aggressive with frequent chemotherapy resistance and a poor prognosis. Therapeutic approaches to advanced-stage or relapsed and refractory disease, including the appropriate sequence of chemotherapy, combined modality therapy, and stem cell transplantation is not well-established. International and multicenter clinical trials are needed for this rare and aggressive disease.

    View details for DOI 10.3109/10428190903186502

    View details for Web of Science ID 000272145000014

    View details for PubMedID 19883307

  • Dynamic CD8 T-Cell Responses to Tumor-Associated Epstein-Barr Virus Antigens in Patients With Epstein-Barr Virus-Negative Hodgkin's Disease ONCOLOGY RESEARCH Kohrt, H., Johannsen, A., Hoppe, R., Horning, S. J., Rosenberg, S. A., Advani, R., Lee, P. P. 2009; 18 (5-6): 287-292

    Abstract

    In almost half of patients diagnosed with Hodgkin's disease (HD), the malignant Reed-Sternberg (RS) cells express Epstein-Barr virus (EBV) antigens. Multiple translational efforts are actively investigating antitumor immune strategies by stimulating cytotoxic T lymphocytes (CTL) against tumor-associated EBV antigens. It has previously been believed that this therapeutic strategy and presence of EBV-specific CTLs are limited to EBV-positive HD. In an effort to explore the EBV-specific immune response, here we characterize EBV-specific CTL responses to lytic and latent EBV antigens in 12 consecutive EBV carriers with EBV-negative HD. Compared to healthy donors, we detected weak, baseline EBV-specific responses to both lytic and latent antigens by IFN-gamma ELISPOT in patients with EBV-negative HD at diagnosis. Chemoradiotherapy was associated temporally with a decrease EBV-specific responses. At final follow-up (24 months), recovery of EBV-specific CTL responses was observed with robustness of lytic-specific response equivalent to healthy controls. We confirm evidence of EBV-specific CTLs in patients with EBV-negative HD and provide the first report of dynamic variance in this population during treatment. Our observation challenges prior belief that patients with HD remain immunodeficient following therapy and argues that the clinical significance of the EBV-specific immune response in EBV-negative HD should be further investigated.

    View details for DOI 10.3727/096504009X12596189659169

    View details for Web of Science ID 000274459900010

    View details for PubMedID 20225766

  • Indolent primary cutaneous B-cell lymphoma: Experience using systemic rituximab JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Morales, A. V., Advani, R., Horwitz, S. M., Riaz, N., Reddy, S., Hoppe, R. T., Kim, Y. H. 2008; 59 (6): 953-957

    Abstract

    Optimal treatment of indolent primary cutaneous B-cell lymphoma (CBCL), marginal zone lymphoma, and follicle center lymphoma, presenting as multiple lesions, has yet to be established. Rituximab is a chimeric monoclonal IgG1 antibody directed against the CD20 antigen of B cells. Clinical efficacy of systemic rituximab in CBCL has yet to be established.We sought to assess the efficacy of systemic rituximab in the treatment of CBCL.This was a retrospective study of 15 patients with indolent CBCL treated with intravenous rituximab (375 mg/m(2)) as a single agent. Variable maintenance regimen was used in a subset of patients. Responses were categorized as complete response, partial response, stable disease, or progressive disease. The efficacy end points included were objective response rate, time to response, time to progression, and duration of response.Ten patients with follicle center lymphoma and 5 with marginal zone lymphoma were included. The objective response rate was 87% (60% complete response, 27% partial response). All patients with follicle center lymphoma had a response with 80% achieving complete response. Of the patients with marginal zone lymphoma, 3 had a response, one stable disease, and one progressive disease. Median follow-up was 36 months. Median time to response, duration of response, and time to progression was 30 days, 24 months, and 24 months, respectively.The study was limited by the small sample size and retrospective design.This study, although small, suggests that rituximab is a reasonable first-line treatment option for indolent CBCL with multiple lesions where local treatment is not effective or desirable.

    View details for DOI 10.1016/j.jaad.2008.08.005

    View details for Web of Science ID 000261141600006

    View details for PubMedID 18817999

  • Evaluation and management of angioimmunoblastic T-cell lymphoma: a review of current approaches and future strategies. Clinical advances in hematology & oncology : H&O Alizadeh, A. A., Advani, R. H. 2008; 6 (12): 899-909

    Abstract

    Angioimmunoblastic T-cell lymphoma (AITL) is a rare and complex lymphoproliferative disorder, clinically characterized by widespread lymphadenopathy, extranodal disease, immune-mediated hemolysis, and polyclonal hypergammaglobulinemia. Significant progress has been made in the understanding of AITL since its recognition as a clonal T-cell disorder with associated deregulation of B-cells and endothelial cells within a unique malignant microenvironment. However, as the responses to conventional chemotherapy have not been durable, prognosis with current treatment approaches has remained dismal. Here we review the clinical presentation, prognosis, and management of patients with AITL. We discuss recent developments in the understanding of the pathogenesis of AITL at a cellular and molecular level, including the implication of the follicular helper T-cell as the corresponding cell of origin, the roles of Epstein-Barr virus, B-cell deregulation, angiogenesis, and other signaling pathways in AITL, and the therapeutic implications of these findings. Finally, we discuss recent clinical trials and novel treatment approaches in the management of patients with AITL.

    View details for PubMedID 19209140

  • Hodgkin disease/lymphoma. Journal of the National Comprehensive Cancer Network Hoppe, R. T., Advani, R. H., Ambinder, R. F., Bierman, P. J., Bloomfield, C. D., Blum, K., Dabaja, B., Djulbegovic, B., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Hudson, M. M., Kaminski, M. S., Love, G., Maloney, D. G., Mansur, D., Mauch, P. M., Moore, J. O., Schilder, R. J., Weiss, L. M., Winter, J. N., Yahalom, J., Zelenetz, A. D. 2008; 6 (6): 594-622

    View details for PubMedID 18597713

  • Paraffin-based 6-gene model predicts outcome in diffuse large B-cell lymphoma patients treated with R-CHOP BLOOD Malumbres, R., Chen, J., Tibshirani, R., Johnson, N. A., Sehn, L. H., Natkunam, Y., Briones, J., Advani, R., Connors, J. M., Byrne, G. E., Levy, R., Gascoyne, R. D., Lossos, I. S. 2008; 111 (12): 5509-5514

    Abstract

    Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by variable clinical outcomes. Outcome prediction at the time of diagnosis is of paramount importance. Previously, we constructed a 6-gene model for outcome prediction of DLBCL patients treated with anthracycline-based chemotherapies. However, the standard therapy has evolved into rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). Herein, we evaluated the predictive power of a paraffin-based 6-gene model in R-CHOP-treated DLBCL patients. RNA was successfully extracted from 132 formalin-fixed paraffin-embedded (FFPE) specimens. Expression of the 6 genes comprising the model was measured and the mortality predictor score was calculated for each patient. The mortality predictor score divided patients into low-risk (below median) and high-risk (above median) subgroups with significantly different overall survival (OS; P = .002) and progression-free survival (PFS; P = .038). The model also predicted OS and PFS when the mortality predictor score was considered as a continuous variable (P = .002 and .010, respectively) and was independent of the IPI for prediction of OS (P = .008). These findings demonstrate that the prognostic value of the 6-gene model remains significant in the era of R-CHOP treatment and that the model can be applied to routine FFPE tissue from initial diagnostic biopsies.

    View details for DOI 10.1182/blood-2008-02-136374

    View details for Web of Science ID 000256786500021

    View details for PubMedID 18445689

  • Beyond the guidelines in the treatment of peripheral T-cell lymphoma: new drug development. Journal of the National Comprehensive Cancer Network Chen, A. I., Advani, R. H. 2008; 6 (4): 428-435

    Abstract

    Peripheral T-cell lymphomas (PTCLs) are a rare and diverse group of neoplasms with a poor prognosis. Management of these disorders has been largely extrapolated from the treatment of aggressive B-cell lymphomas; however, therapeutic responses to this approach are neither adequate nor durable for most patients with PTCL. Given the rarity of PTCL, much of the literature consists of studies with small sample size and anecdotal case reports. Therefore, no consensus exists on the best therapeutic strategy for either newly diagnosed or relapsed/refractory PTCL. This article reviews promising novel approaches in the treatment of PTCL and its subtypes. Investigation into the pathogenesis of PTCL has also identified new targets for treatment. These emerging therapies include new uses of existing agents and the development of novel agents specifically targeted against T-cell lymphoma. Results using antimetabolites, immunotherapies, and histone deacetylase inhibitors have been particularly encouraging. These novel therapies are being tested as single agents and in combination with conventional lymphoma regimens in the frontline and salvage settings. Because of the rarity and heterogeneity of PTCL, national and international cooperation is needed to conduct the clinical studies required for the development of more effective treatment paradigms. These efforts are ongoing and will hopefully guide new strategies to improve the historically poor outcome of PTCL.

    View details for PubMedID 18433608

  • Non-Hodgkin's lymphomas. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Advani, R. H., Byrd, J. C., Czuczman, M. S., Damon, L. E., Duvic, M., Fayad, L., Forero, A., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Horwitz, S. M., Kaminski, M. S., Kim, Y. H., LaCasce, A. S., Nademanee, A., Olsen, E. A., Porcu, P., Press, O., Prosnitz, L., Smith, M. R., Sotomayor, E. M., Vose, J. M., Yahalom, J., Yunus, F. 2008; 6 (4): 356-421

    View details for PubMedID 18433606

  • Non-Hodgkin lymphoma of the breast CANCER Ganjoo, K., Advani, R., Mariappan, M. R., McMillan, A., Horning, S. 2007; 110 (1): 25-30

    Abstract

    Primary lymphoma of the breast has been reported to have a high local and central nervous system recurrence (CNS) rate, suggesting the need for consolidation radiotherapy and CNS prophylaxis. A retrospective study was done to evaluate the institutional experience in this patient population.In all, 37 patients with lymphoma involving the breast at initial diagnosis and managed at Stanford University from 1981-2005 were included. Diagnostic tissue biopsies were obtained either from the breast mass or an involved lymph node. Treatment and response data, patterns of recurrence, and outcomes were reviewed.Diffuse large B cell lymphoma (DLBCL) was the most common histologic subtype seen in 18 of 37 (49%) patients. Follicular and marginal zone subtypes were seen in 38%. Most patients presented with an incidental breast mass in stage I(E) or II(E). Four (11%) patients presented with bilateral breast involvement, with only 1 patient presenting with CNS disease. DLBCL patients received doxorubicin-based chemotherapy, with 70% receiving involved field radiotherapy and a single patient receiving intrathecal therapy. No recurrences occurred in the involved breast and a single parenchymal CNS recurrence was recorded. Among the DLBCL patients, the 5-year progression-free survival (PFS) was 61%, with a median follow-up of 3.8 years (range, 5 months to 19 years) and the 5-year overall survival (OS) was estimated at 82%. Patients with indolent lymphoma had an estimated 5-year PFS of 76% and an OS of 92%.DLBCL of the breast was successfully treated with doxorubicin-based chemotherapy alone or with involved field radiotherapy in an estimated 61% of patients at 5 years. A single CNS recurrence was observed in our series of patients, most of whom presented with limited disease.

    View details for DOI 10.1002/cncr.22753

    View details for Web of Science ID 000247384200003

    View details for PubMedID 17541937

  • Treatment of mantle cell lymphoma: Current approach and future directions CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY Brody, J., Advani, R. 2006; 58 (3): 257-265

    Abstract

    Although mantle cell lymphoma has been described as "moderately aggressive" it has become clear that it carries a worse long-term prognosis than other subtypes of non-Hodgkin's lymphoma. In recent years, this has prompted numerous clinical trials of novel and more aggressive therapies in hopes of impacting these poor outcomes. These include more intensive combination chemotherapy regimens, monoclonal antibody therapy in conjunction with other treatments or conjugated to radioactive isotopes, high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation, and newer targeted therapies based on increasing understanding of the molecular pathways of this malignancy.

    View details for DOI 10.1016/j.critrevonc.2005.10.001

    View details for Web of Science ID 000238633200007

    View details for PubMedID 16751087

  • Staging accuracy in mycosis fungoides and Sezary syndrome using integrated positron emission tomography and computed tomography ARCHIVES OF DERMATOLOGY Tsai, E. Y., Taur, A., Espinosa, L., Quon, A., Johnson, D., Dick, S., Chow, S., Advani, R., Warnke, R., Kohler, S., Hoppe, R. T., Kim, Y. H. 2006; 142 (5): 577-584

    Abstract

    To evaluate the usefulness of integrated positron emission tomography and computed tomography (PET/CT) in staging mycosis fungoides (MF) and Sézary syndrome and to correlate PET/CT data with histopathologic diagnosis of lymph nodes (LNs).A single-center, prospective cohort analysis.Academic referral center for cutaneous lymphoma.Thirteen patients with MF and SS at risk for secondary LN involvement. Interventions Patients were clinically evaluated based on general physical examination, total body skin examination, and laboratory screening. They underwent integrated PET/CT followed by excisional biopsy of LNs.We used PET/CT to assess LN size and metabolic activity. Enlarged LNs were defined as axillary or inguinal LNs with a short axis 1.5 cm or larger; or cervical LN, with a short axis 1.0 cm or larger. We classified LN pathologic results according to National Cancer Institute (LN1-4) and World Health Organization (WHO 1-3) criteria. We quantified PET activity using standardized uptake value (SUV) and correlated with LN grade.Based on CT size criteria alone, only 5 patients had enlarged LNs, whereas PET revealed hypermetabolic LNs in all 13 patients. Six patients had LN1-3, and 7 had effacement of LN architecture by lymphoma cells (LN4). Of the 7 patients with LN4 nodes, 4 had SS, and 3 had tumorous MF. Two patients with LN4 nodes had inguinal LNs smaller than 1.5 cm and would have been assigned an N0 classification without the use of integrated PET/CT. Correlation of SUV with LN grade revealed that LN1-3 nodes were associated with a mean SUV of 2.7 (median SUV, 2.2; range, 2.0-4.7) and LN4 nodes were associated with a mean SUV of 5.4 (median SUV, 3.9; range, 2.1-11.8). Patients with large cell transformation had the highest SUVs.For staging MF and SS, PET/CT was more sensitive in detecting LN involved by lymphoma compared with CT data alone and thus may provide more accurate staging and prognostic information. The intensity of PET activity correlated with histologic LN grade.

    View details for Web of Science ID 000237543100006

    View details for PubMedID 16702495

  • Non-Hodgkin's lymphoma. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Zelenetz, A. D., Advani, R. H., Buadi, F., Cabanillas, F., Caligiuri, M. A., Czuczman, M. S., Damon, L. E., Fayad, L., Flinn, I. W., Forero, A., Glenn, M. J., Gockerman, J. P., Gordon, L. I., Harris, N. L., Hoppe, R. T., Kaminski, M. S., LaCasce, A. S., Nademanee, A., Porcu, P., Press, O., Prosnitz, L., Smith, M. R., Sotomayor, E. M., Vose, J. M., Yahalom, J. 2006; 4 (3): 258-310

    View details for PubMedID 16507273

  • Hodgkin disease/lymphoma. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Hoppe, R. T., Advani, R. H., Bierman, P. J., Bloomfield, C. D., Buadi, F., Djulgegovic, B., Forero, A., Gordon, L. I., Hernandez-Ilizaliturri, F. J., Kaminski, M. S., Love, G., Maloney, D. G., Mauch, P. M., Moore, J. O., Schilder, R. J., Weiss, L., Winter, J. N., Yahalom, J., Zelenetz, A. D. 2006; 4 (3): 210-230

    View details for PubMedID 16507269

  • Management of advanced stage Hodgkin lymphoma. Journal of the National Comprehensive Cancer Network Advani, R., Ai, W. Z., Horning, S. J. 2006; 4 (3): 241-247

    Abstract

    Although advanced Hodgkin lymphoma is highly curable, balancing the high cure rate with long-term toxicity is challenging. ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) is the standard chemotherapy regimen, producing a high cure rate with acceptable toxicity. Stanford V and BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) are new regimens with encouraging results and are undergoing randomized clinical trials. The International Prognostic Score provides a clinical tool that may help identify patients with high-risk disease who may require a more aggressive regimen. Consolidative radiation's role in managing advanced Hodgkin lymphoma is still controversial, but it is most accepted for bulky or residual disease or after brief chemotherapy. The development and integration of newer imaging tools, such as fluorodeoxyglucose-positron emission tomography imaging, may allow a more precise evaluation of disease and help define which patients might benefit from consolidative treatment.

    View details for PubMedID 16507271

  • A phase I trial of liposomal doxorubicin, paclitaxel and valspodar (PSC-833), an inhibitor of multidrug resistance ANNALS OF ONCOLOGY Advani, R., Lum, B. L., Fisher, G. A., Halsey, J., Chin, D. L., Jacobs, C. D., Sikic, B. I. 2005; 16 (12): 1968-1973

    Abstract

    The aim of this study was to determine (i) the maximum tolerated dose (MTD) of liposomal doxorubicin (L-DOX) and paclitaxel (DP), (ii) the MTD of DP plus valspodar (DPV) and (iii) pharmacokinetic (PK) interactions of valspodar with L-DOX and paclitaxel.Twenty-three patients with metastatic cancers received DP, followed 4 weeks later by DPV. Dose levels of DP were (mg/m2 for L-DOX/paclitaxel): 30/135 (n = 7), 30/150 (n = 4), 35/150 (n = 8) and 40/150 (n = 4). Dose levels of DPV were 15/70 (n = 10) and 15/60 (n = 10). Serial, paired PK studies were performed.The MTD of DP was 40/150. For DPV at 15/70, five of 10 patients experienced grade 4 neutropenia. In the next cohort, a reduced dose of 15/60 was well tolerated. Valspodar produced reversible grade 3 ataxia in seven patients, requiring dose reduction from 5 to 4 mg/kg. Paired PK studies indicated no interaction between L-DOX and valspodar, and a 49% increase in the median half-life of paclitaxel. Two partial and one minor remissions were noted.The use of valspodar necessitated dose reductions of DP, with neutropenia being dose limiting. Valspodar PK interactions were observed with paclitaxel but not L-DOX.

    View details for DOI 10.1093/annonc/mdi396

    View details for Web of Science ID 000233489600018

    View details for PubMedID 16126736

  • A phase I trial of aprinocarsen (ISIS 3521/LY900003), an antisense inhibitor of protein kinase C-alpha administered as a 24-hour weekly infusion schedule in patients with advanced cancer INVESTIGATIONAL NEW DRUGS Advani, R., Lum, B. L., Fisher, G. A., Halsey, J., Geary, R. S., Holmlund, J. T., Kwoh, T. J., DORR, F. A., Sikic, B. I. 2005; 23 (5): 467-477

    Abstract

    A phase I study was performed to determine the maximum tolerated dose (MTD), safety profile and pharmacology of aprinocarsen (ISIS 3521), an antisense oligonucleotide to protein kinase C-alpha, in patients with refractory solid tumors.Fourteen patients were treated in sequential cohorts of aprinocarsen by 24-hour continuous infusion (CIV), weekly, at doses of 6, 12, 18 and 24 mg/kg.One grade 4 toxicity was observed, transient grade 4 neutropenia at 18 mg/kg. Grade 3 toxicities included neutropenia at 12 mg/kg, fever and hemorrhage at 18 mg/kg, and neutropenia, nausea, and chills at 24 mg/kg. Grade 2 toxicities included thrombocytopenia myalgias, chills, headache, fatigue, fever and nausea/vomiting. Mean prothrombin times and activated partial thromboplastin times (aPTT) increased by 10% and 29% from baseline (p = 0.006 and 0.005). Mean complement split products (Bb and C3a) increased 1.6-fold and 3.6-fold (from p = 0.014 and 0.004, respectively). These changes correlated with dose and were transient with recovery to baseline by day 7. Steady state plasma concentrations (Css) of aprinocarsen were achieved within four hours. Css better described changes in aPTT than dose. Clinical evidence of complement activation was not observed.In contrast to 21-day protracted infusion schedules, delivery of aprinocarsen over a 24-hour infusion schedule showed concentration-dependent effects on coagulation and complement, which are consistent with nonclinical toxicology studies performed in the phosphorothioate DNA antisense drug class. These coagulation and complement changes resulted in a maximum tolerated dose 24 mg/kg.

    View details for DOI 10.1007/s10637-005-2906-0

    View details for Web of Science ID 000231245000008

    View details for PubMedID 16133798

  • A Phase I Trial of Aprinocarsen (ISIS 3521/LY900003), an Antisense Inhibitor of Protein Kinase C-alpha Administered as a 24-hour Weekly Infusion Schedule in Patients with Advanced Cancer. Investigational New Drugs, Advani R, Lum BL, Fisher GA, Halsey J, Geary RS, Holmlund JT, Kwoh TJ, Dorr FA, Sikic BI. 2005; In Press
  • Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: A phase III trial (E2995) JOURNAL OF CLINICAL ONCOLOGY Greenberg, P. L., Lee, S. J., Advani, R., Tallman, M. S., Sikic, B. I., Letendre, L., Dugan, K., Lum, B., Chin, D. L., Dewald, G., Paietta, E., Bennett, J. M., Rowe, J. M. 2004; 22 (6): 1078-1086

    Abstract

    To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator valspodar (PSC 833; Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).A phase III randomized study was performed using valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n=66) versus MEC (n=63) to treat patients with relapsed or refractory AML and high-risk MDS.For the PSC-MEC versus MEC arms, complete response (CR) was achieved in 17% versus 25% of patients, respectively (P=not significant). For patients who had not received prior intensive chemotherapy (ie, with secondary AML or high-risk MDS), the CR rate was increased--35% versus 15% for the remaining patients (P=.018); CR rates did not differ between treatment arms. The median disease-free survival in those achieving CR was similar in the two arms (10 versus 9.3 months) as was the patients' overall survival (4.6 versus 5.4 months). The CR rates in MDR+ (69% of patients) versus MDR- patients were similar for those receiving either chemotherapy regimen (16% versus 24%). The CR rate for unfavorable cytogenetic patients (45% of patients) was 13% compared to the remainder, 28% (P=.09). Population pharmacokinetic analysis demonstrated that the clearances of mitoxantrone and etoposide were decreased by 59% and 50%, respectively, supporting the empiric dose reductions in the PSC-MEC arm designed in anticipation of drug interactions between valspodar and the chemotherapeutic agents.CR rates and overall survival were not improved by using PSC-MEC compared to MEC chemotherapy alone in patients with poor-risk AML or high-risk MDS.

    View details for DOI 10.1200/JCO.2004.07.048

    View details for Web of Science ID 000220287900017

    View details for PubMedID 15020609

  • Phase I and pharmacokinetic study of BMS-188797, a new taxane analog, administered on a weekly schedule in patients with advanced malignancies CLINICAL CANCER RESEARCH Advani, R., Fisher, G. A., Lum, B. L., Jambalos, C., Cho, C. D., Cohen, M., Gollerkeri, A., Sikic, B. I. 2003; 9 (14): 5187-5194

    Abstract

    The purpose of this study was to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary activity of BMS-188797 administered weekly.Patients with advanced malignancies were treated with escalating doses of BMS-188797 on a weekly schedule as a 1-h i.v. infusion. Plasma sampling was performed to characterize the pharmacokinetics of BMS-188797.Eighteen patients with advanced malignancies were enrolled at three dose levels ranging from 35 to 65 mg/m(2). The number of patients evaluated at each dose level was as follows: 35 mg/m(2) (n = 3); 50 mg/m(2) (n = 9); and 65 mg/m(2) (n = 6). At 65 mg/m(2), three of six patients had a DLT (one had grade 4 neutropenia lasting >7 days, and two had grade 3 diarrhea). Expansion of the 50-mg/m(2) dose cohort to nine patients established this dose as the MTD, with one patient experiencing a DLT (grade 4 neutropenia with fever). Two partial responses were observed (lung cancer, 7+ months; ovarian cancer, 6+ months durations), as well as two minor responses (esophageal cancer, 5 months; ovarian cancer, 5 months). Both patients with partial responses had been clinically resistant to paclitaxel. Plasma pharmacokinetic mean values of maximum concentration (C(max)) and area under the curve (AUC(0-48)) increased in a dose-dependent manner within the range of doses used in this study, and in three of four patients, the DLTs correlated with AUC.The MTD and the recommended Phase II dose of weekly BMS-188797 is 50 mg/m(2). The drug demonstrates antitumor activity in taxane-refractory solid tumors and is now being evaluated in combination with carboplatin.

    View details for Web of Science ID 000186558400017

    View details for PubMedID 14613998

  • Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood Advani R, Saba HI, Tallman M, Rowe JM, Wiernik PH, Ramek J, Dugan K, Lum B, Villena J, Sikic BI, Davis E, Paietta E, Litchman M , Greenberg P. 1999; 93: 787-95

Conference Proceedings


  • Prediction of Survival In Diffuse Large B-Cell Lymphoma Based On the Expression of Two Genes Reflecting Tumor and Microenvironment Alizadeh, A. A., Gentles, A. J., Alencar, A. J., Kohrt, H. E., Houot, R., Goldstein, M. J., Zhao, S., Natkunam, Y., Advani, R., Gascoyne, R. D., Briones, J., Tibshirani, R. J., Myklebust, J. H., Plevritis, S. K., Lossos, I. S., Levy, R. AMER SOC HEMATOLOGY. 2010: 836-837
  • Prognostic significance of vascular endothelial growth factor (VEGF), VEGF receptors (VEGFR), and vascularity in diffuse large B-cell lymphoma treated with immunochemotherapy (R-CHOP) Gratzinger, D., Advani, R., Zhao, S., Talreja, N., Tibshirani, R. J., Horning, S. J., Levy, R., Lossos, I. S., Gascoyne, R. D., Natkunam, Y. AMER SOC CLINICAL ONCOLOGY. 2009
  • A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance Advani, R., Fisher, G. A., Lum, B. L., Hausdorff, J., Halsey, J., Litchman, M., Sikic, B. I. AMER ASSOC CANCER RESEARCH. 2001: 1221-1229

    Abstract

    P-glycoprotein is an efflux pump for many drugs including doxorubicin and paclitaxel. This study evaluated the coadministration of these drugs with the P-glycoprotein inhibitor valspodar (PSC 833) with the aim of determining: (a) maximum tolerated doses (MTDs) of doxorubicin followed by paclitaxel (DP); (b) the MTD of DP combined with PSC 833 (DPV), without and with filgrastim (G-CSF); and (c) the pharmacokinetic interactions of PSC 833 with doxorubicin and paclitaxel.For the first cycle, patients received doxorubicin as a 15-min infusion followed by paclitaxel as a 1-h infusion. For the second cycle, patients received reduced doses of DP with PSC 833 at 5 mg/kg p.o., four times a day for 12 doses.Thirty-three patients with various refractory malignancies were enrolled and assessable. The MTD of DP without PSC 833 was 35 mg/m(2) doxorubicin and 150 mg/m(2) paclitaxel. The MTD of DPV without G-CSF was 12.5 mg/m(2) doxorubicin and 70 mg/m(2) paclitaxel. The dose-limiting toxicity for both DP and DPV was neutropenia without thrombocytopenia. With G-CSF, the MTD for DPV was 20 mg/m(2) doxorubicin and 90 mg/m(2) paclitaxel. No grade 4 nonhematological toxicities were observed. Five partial and two minor tumor remissions were observed. Paired pharmacokinetics with and without PSC 833 revealed substantial drug interactions with both doxorubicin and paclitaxel.PSC 833 can be administered safely with doxorubicin and paclitaxel. The pharmacokinetic profiles of these drugs are significantly affected by PSC 833, requiring approximately 60% dose reductions for equivalent degrees of myelosuppression.

    View details for Web of Science ID 000168768500018

    View details for PubMedID 11350887

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