Fludarabine and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Lymphocytic Leukemia or Waldenstrom's Macroglobulinemia
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|ClinicalTrials.gov Identifier: NCT00281983|
Recruitment Status : Completed
First Posted : January 25, 2006
Last Update Posted : July 24, 2017
RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.
PURPOSE: This phase I/II trial is studying the side effects of giving fludarabine together with cyclophosphamide and to see how well they work in treating patients who are undergoing donor stem cell transplant for B-cell chronic lymphocytic leukemia or Waldenström's macroglobulinemia.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Biological: alemtuzumab Biological: anti-thymocyte globulin Biological: filgrastim Biological: rituximab Biological: therapeutic allogeneic lymphocytes Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy||Phase 1 Phase 2|
- Determine the feasibility and safety of induction therapy comprising fludarabine and cyclophosphamide followed by allogeneic stem cell transplantation in patients with high-risk B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma (Waldenstrom's macroglobulinemia).
- Determine the incidence and kinetics of clinical and molecular remissions in patients treated with this regimen.
- Determine event-free and overall survival of patients treated with this regimen.
- Determine the duration of clinical and molecular remission in relation to the underlying cytogenetic deviation in patients treated with this regimen.
- Determine the kinetics and extent of lympho-hematopoietic donor chimerism in patients treated with this regimen.
OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.
- Cytoreductive therapy: Patients receive up to 3 courses of cytoreductive therapy comprising fludarabine IV and cyclophosphamide IV on days 1-3 (with or without rituximab IV on day 1). Patients refractory to fludarabine-containing therapy may receive alemtuzumab IV for 12 weeks OR any other cytotoxic salvage regimen for cytoreduction.
- Conditioning regimen: Patients receive 1 of the following conditioning regimens*:
NOTE: *Patients who did not achieve partial response after cytoreductive therapy receive regimen 3.
- Regimen 1: Patients receive fludarabine IV and cyclophosphamide IV on days -7 to -3. If stem cells are collected from an unrelated donor, patients also receive anti-thymocyte globulin (ATG) IV on days -4 to -1.
- Regimen 2: Patients undergo total-body irradiation on day -9. Patients then receive alemtuzumab IV on days -8 to -4 and fludarabine IV and cyclophosphamide IV on days -6 to -2.
Regimen 3: Patients receive fludarabine IV on days -7 to -3, busulfan IV or orally on days -7 to -5, and cyclophosphamide IV on days -3 to -2. If stem cells are collected from an unrelated donor, patients also receive ATG on days -3 to -1.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily starting on day 5 and continuing until blood count recover.
- Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV beginning on day -1 and continuing until approximately day 100. Patients treated with conditioning regimen 1 or 3 also receive methotrexate IV on days 1, 3, and 6 OR oral mycophenolate mofetil twice daily on days 0-50. Patients with evidence of residual disease at least 4 weeks after completion of cyclosporine undergo donor lymphocyte infusion (DLI).
- DLI: The donor T-lymphocytes are collected from the PBSCT donor without prior G-CSF mobilization. Patients receive DLI every 8 weeks in the presence of residual disease and the absence of GVHD.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia|
|Study Start Date :||June 2000|
|Study Completion Date :||July 2010|
Experimental: Allogeneic stem cell transplantation
||Biological: alemtuzumab Biological: anti-thymocyte globulin Biological: filgrastim Biological: rituximab Biological: therapeutic allogeneic lymphocytes Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy|
- Feasibility as measured by the proportion of eligible patients completing the transplant procedure successfully
- Safety as measured by a treatment-related mortality of < 25% at 2 years following transplant
- Clinical remission rate by NIH criteria at 12 months following transplant
- Minimal residual disease negativity rate as measured by high-resolution flow or CDR PCR at 12 months following transplant
- Chimerism as measured by STR-PCR at 12 months following transplant
- Event-free and overall survival at 5 years following transplant
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00281983
|Montreal, Quebec, Canada, H1T 2M4|
|Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin|
|Berlin, Germany, 12200|
|Essen, Germany, 45122|
|Goettingen, Germany, 37075|
|Asklepios Klinik St. Georg|
|Hamburg, Germany, D-20099|
|Medizinische Hochschule Hannover|
|Hannover, Germany, 30625|
|Heidelberg, Germany, D-69120|
|Universitaetsklinikum des Saarlandes|
|Homburg, Germany, 66421|
|Clinic for Bone Marrow Transplantation and Hematology and Oncology|
|Idar-Oberstein, Germany, D-55743|
|University Hospital Schleswig-Holstein - Kiel Campus|
|Kiel, Germany, 24116|
|University Hospital of Leipzig|
|Leipzig, Germany, 04103|
|Klinikum der Universitaet Regensburg|
|Regensburg, Germany, 93053|
|Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm|
|Ulm, Germany, 89081|
|Study Chair:||Peter Dreger||Universitaets-Kinderklinik Heidelberg|