Robert Lowsky
TLI & ATG for Non-Myeloablative Allogeneic Transplantation for MDS and MPD
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients with advanced stage MDS and MPD.
Recruiting Status:
RecruitingStanford Recruiting Status:
RecruitingIntervention(s):
- Procedure: Total Lymphoid Irradiation
- Procedure: Anti-Thymocyte Globulin as Conditioning
Phase:
Phase 2Eligibility
Ages Eligible for Study:
49 years to 75 yearsGenders Eligible for Study:
Male and FemaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
GENERAL INCLUSION CRITERIA
- General inclusion criteria must include at least one of the following:
o Patients aged > 49 and < 75 years with MDS or MPD
o Patients aged < 49 years at high risk for regimen related toxicity using standard high dose regimens. Factors considered high risk include pre-existing conditions such as a chronic disease affecting kidneys, liver, lungs, or heart.
o Patients with secondary MDS following a prior autologous transplant.
- An HLA-identical related or an HLA-matched unrelated donor is available. ABO incompatibility is acceptable.
- A signed informed consent form.
MYELODYSPLASTIC SYNDROME CRITERIA
- Diagnosis of MDS classifiable by the FAB system as refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), chronic myelomonocytic leukemia (CMML), refractory anemia with excess blasts (RAEB), and MDS transformed to acute leukemia.
- Patients with advanced MDS must be cytoreduced to < 10% marrow blasts prior to receiving conditioning with TLI/ATG. Less than 10% marrow blasts must be documented by marrow examination within 1 month of starting conditioning. The cytoreductive regimen will be determined by referring centers.
- Patients with evolution to AML are required to be in a complete remission as defined by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable.
- All patients with high risk disease, for example "intermediate-2" or "high risk" disease by the IPSS score. Other selected patients with a lower IPSS score may be considered but only after discussion with the BMT attending physicians, as a group, and the PI of the study.
MYELOPROLIFERATIVE DISORDERS
- Myeloproliferative disorders to be included:
o Philadelphia chromosome-negative CML.
o Patients with polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to post-polycythemic marrow fibrosis.
o Patients with essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to myelofibrosis.
o Patients with agnogenic myeloid metaplasia with high risk disease, for example "intermediate" or "high risk" according to the Lille Scoring System.
- Patients must be cytoreduced to < 10% marrow blasts. Less than 10% marrow blasts must be documented by marrow examination within 1 month of initiation of TLI/ATG. The cytoreductive regimen will be determined by referring centers.
- Patients with evolution to AML are required to be in a complete remission as defined by a blast count of less than 5% in a marrow aspirate with adequate cellularity. Presence of residual dysplastic features following cytoreductive therapy is acceptable.
INCLUSION CRITERIA - RELATED DONORS
- Related to the patient and is genotypically or phenotypically HLA-identical.
- Donor age < 75 unless cleared by P.I
- Capable of giving written, informed consent.
- Donor must consent to PBSC mobilization with G-CSF and apheresis
INCLUSION CRITERIA - UNRELATED DONORS
- Donors must be HLA-matched as defined by the following criteria:
o Matched for HLA-DRB1 and DQB1 by high resolution typing.
o Serologic match for all recognized HLA-A, HLA-B, and HLA-C antigens, and molecular match for at least 5 of 6 HLA-A, HLA-B, or HLA-C antigens by high resolution typing.
- Donor must consent to PBSC mobilization with G-CSF and apheresis. Bone marrow unrelated donors are not eligible for this protocol.
Key Exclusion Criteria:
GENERAL EXCLUSION CRITERIA
- Organ dysfunction as defined by the following:
o Renal: Patients with a normal creatinine are eligible for study without the need for a 24 hr urine collection for creatinine clearance. Patients with an elevated creatinine require a 24 hr urine collection. If the creatinine clearance is < 50 ml/min patients will be determined for inclusion on a case by case basis.
o Cardiac: Ejection fraction < 40%, symptomatic congestive heart failure requiring therapy, poorly controlled cardiac arrythmias, or poorly controlled hypertension with inability to maintain a steady-state blood pressure of 150/90.
o Pulmonary: Requirement for supplemental oxygen administration, or pulmonary function testing showing (1) DLCO < 50% of predicted, (2) TLC < 30%, or (3) FEV1 < 30%.
o Hepatic: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function and degree of portal hypertension. Patients will be excluded if they are found to have fulminant liver failure, cirrhosis if the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess. Biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, and symptomatic biliary disease.
- Bone marrow documenting blast count >=10%.
- Presence of active of non-hematologic malignancy (except localized non-melanoma skin malignancies) or hematologic malignancy other than MDS or MPD as listed in inclusion criteria.
- Active CNS involvement of disease.
- Karnofsky performance score <= 60% or Lansky-Play Performance score <50 for pediatric patients.
- Life expectancy severely limited by diseases other than malignancy.
- Fungal infections with radiological progression despite with an amphotericin product or active triazole for > 1 month.
- Active bacterial infection.
- Patients of fertile age who refuse contraception for a twelve month period post-transplant.
- Pregnant or lactating females.
- HIV seropositivity.
- Severe psychological illness.
EXCLUSION CRITERIA - RELATED DONORS
- Identical twin
- Any contra-indication to the administration of subcutaneous G-CSF at a dose of 16mg/kg/d for five consecutive days
- Serious medical or psychological illness
- Pregnant or lactating females
- Prior malignancy within the preceding five years, with the exception of non-melanoma skin cancers.
- HIV seropositivity
Additional Study Details
Official Title:
Total Lymphoid Irradiation and Anti-Thymocyte Globulin as Conditioning for Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation for the Treatment of Myelodysplastic Syndromes and Myeloproliferative Disorders (except CML)Anticipated start date:
7/6/2004Lead Sponsor:
Stanford UniversityCollaborator(s):
- National Institutes of Health (NIH), PPG
Investigator(s):
Study Type:
InterventionalPurpose:
TreatmentAllocation:
Non-randomizedMasking:
OpenControl:
noneAssignment:
Single GroupEndpoints:
Safety/EfficacyPrimary Outcomes:
- To improve survival outcome for selected patients with advanced stages of MDS and MPD with non-myeloablative allogeneic HCT from related and unrelated donors.
- To evaluate the feasibility and safety of TLI/ATG conditioning for allogeneic HCT for elderly patients or those with co-morbid conditions that preclude myeloablative transplantation for advanced stage MDS and MPD.
Secondary Outcomes:
- To evaluate myeloid and platelet engraftment.
- To evaluate the incidence of acute and chronic GVHD.
- To evaluate the rate of primary and secondary graft failure.
- To evaluate the rate of relapse, survival and event-free survival.
- To evaluate if DLI can be used safely in patients with mixed chimerism.
Total Number to be Enrolled:
34Total Number to be Enrolled at Stanford:
34More Information
Secondary ID(s):
- 95130
- BMT168
- NCT00185796
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
8/19/2009PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
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