CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia

This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating patients with CD19 positive diffuse large B-cell lymphoma or B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on diffuse large B-cell lymphoma and B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating patients with diffuse large B-cell lymphoma or B acute lymphoblastic leukemia.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Crystal Mackall, MD

Stanford Investigator(s):

Intervention(s):

  • Biological: Chimeric Antigen Receptor T-Cell Therapy
  • Drug: Cyclophosphamide
  • Drug: Fludarabine Phosphate
  • Other: Laboratory Biomarker Analysis
  • Other: Questionnaire Administration

Phase:

Phase 1

Eligibility


Inclusion Criteria:

   - For diffuse large B-cell lymphoma (DLBCL)

      - Histologically confirmed aggressive B cell non-Hodgkin lymphoma (NHL) including
      the following types defined by World Health Organization (WHO) 2008:

         - DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma;
         DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL
         of the elderly; OR

         - Primary mediastinal (thymic) large B cell lymphoma

         - Transformation of follicular lymphoma to DLBCL will also be included

      - Subjects with DLBCL must have progressed, had stable disease (SD), or recurred
      after initial treatment regimens that include an anthracycline and an anti CD20
      monoclonal antibody; subjects who relapse >= 12 months after therapy should have
      progressed after autologous transplant or been ineligible for autologous
      transplant

   - For B acute lymphoblastic leukemia (ALL)

      - Chemotherapy refractory disease in subjects with B-ALL is defined as progression
      or stable disease after two lines of standard therapies (two induction regimens),
      or relapsed disease after 2 established induction regimens

      - Subjects with persistent or relapsed minimal residual disease (MRD) / next
      generation sequencing (NGS) relapse require verification of relapse on two
      occasions at least 4 weeks apart

      - Subjects with Philadelphia chromosome positive acute lymphoblastic leukemia
      (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed
      after two lines of therapy, including tyrosine kinase inhibitors (TKIs)

   - CD19 expression is required and must be detected on greater than 50% of the malignant
   cells by immunohistochemistry or >= 90% by flow cytometry; the choice of whether to
   use flow cytometry or immunohistochemistry will be determined by what is the most
   easily available tissue sample in each subject; in general, immunohistochemistry will
   be used for lymph node biopsies, flow cytometry will be used for peripheral blood and
   bone marrow samples

   - Subjects who have undergone autologous stem cell transplantation (SCT) with disease
   progression or relapse following SCT are eligible; subjects who have undergone
   allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria,
   they are at least 100 days post transplant, they have no evidence of graft versus host
   disease (GVHD) and have been without immunosuppressive agents for at least 30 days

   - Must have evaluable or measurable disease according to the revised International
   Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been
   previously irradiated will be considered measurable only if progression has been
   documented following completion of radiation therapy

   - At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any
   prior systemic therapy at the time the subject is planned for leukapheresis, except
   for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5
   half-lives

   - Toxicities due to prior therapy must be stable and recovered to =< grade 1 (except for
   clinically non significant toxicities such as alopecia)

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, or Karnofsky
   >= 80%

   - Absolute neutrophil count (ANC) >= 750/uL

   - Platelet count >= 50,000/uL

   - Absolute lymphocyte count >= 150/uL

   - Creatinine =< 2 mg/dL or creatinine clearance (as estimated by Cockcroft Gault
   equation) >= 60 mL/min

   - Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 upper
   limit of normal (ULN)

   - Total bilirubin =< 1.5 mg/dl, except in subjects with Gilbert?s syndrome

   - Cardiac ejection fraction >= 45%, no evidence of physiologically significant
   pericardial effusion as determined by an echocardiogram (ECHO), and no clinically
   significant electrocardiogram (ECG) findings

   - No clinically significant pleural effusion

   - Baseline oxygen saturation > 92% on room air

   - Central nervous system (CNS) status

      - Subjects with ALL

         - Subjects with the following CNS status are eligible only in the absence of
         neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

            - CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on
            cytospin preparation, regardless of the number of white blood cells
            (WBCs);

            - CNS 2, defined as presence of < 5/uL WBCs in CSF and cytospin positive
            for blasts, or > 5/uL WBCs but negative by Steinherz/Bleyer algorithm:

               - CNS 2a: < 10/uL red blood cells (RBCs); < 5/uL WBCs and cytospin
               positive for blasts;

               - CNS 2b: >= 10/uL RBCs; < 5/uL WBCs and cytospin positive for
               blasts;

               - CNS 2c: >= 10/uL RBCs; >= 5/uL WBCs and cytospin positive for
               blasts but negative by Steinherz/Bleyer algorithm

      - Subjects with DLBCL

         - Subjects must have no signs or symptoms of CNS disease or detectable
         evidence of CNS disease on magnetic resonance imaging (MRI) at the time of
         screening; subjects who have been previously treated for CNS disease but
         have no evidence of disease at screening are eligible

   - Females of childbearing potential must have a negative serum or urine pregnancy test
   (females who have undergone surgical sterilization or who have been postmenopausal for
   at least 2 years are not considered to be of childbearing potential)

   - Subjects of child bearing or child fathering potential must be willing to practice
   birth control from the time of enrollment on this study and for four (4) months after
   receiving the preparative regimen; females of child bearing potential must have a
   negative pregnancy test

   - Must be able to give informed consent; subjects unable to give informed consent will
   not be eligible for this study

Exclusion Criteria:

   - History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g.
   cervix, bladder, breast) unless disease free for at least 3 years

   - History of Richter?s transformation of chronic lymphocytic leukemia (CLL)

   - Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
   requiring IV antimicrobials for management; simple urinary tract infection (UTI) and
   uncomplicated bacterial pharyngitis are permitted if responding to active treatment;
   known history of infection with human immunodeficiency virus (HIV) or hepatitis B
   (hepatitis B surface antigen [HBsAg] positive) or hepatitis C virus (anti hepatitis C
   virus [HCV] positive); a history of hepatitis B or hepatitis C is permitted if the
   viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or
   nucleic acid testing

   - History or presence of CNS disorder such as seizure disorder, cerebrovascular
   ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS
   involvement

   - History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
   other clinically significant cardiac disease within 12 months of enrollment, or have
   cardiac atrial or cardiac ventricular lymphoma involvement

   - Subjects receiving anticoagulation therapy

   - Any medical condition that in the judgement of the sponsor investigator is likely to
   interfere with assessment of safety or efficacy of study treatment

   - History of severe immediate hypersensitivity reaction to any of the agents used in
   this study

   - Women of child bearing potential who are pregnant or breastfeeding; females who have
   undergone surgical sterilization or who have been postmenopausal for at least 2 years
   are not considered to be of childbearing potential

   - In the investigators judgment, the subject is unlikely to complete all protocol
   required study visits or procedures, including follow up visits, or comply with the
   study requirements for participation

   - May not have primary immunodeficiency or history of autoimmune disease (e.g. Crohns,
   rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring
   systemic immunosuppression/systemic disease modifying agents within the last 2 years

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Matthew Abramian
650-736-3351
Recruiting

New Trial Alerts

Receive email alerts when trials open to patients.