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RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic breast cancer, or kidney cancer.
OBJECTIVES: * Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and durable donor engraftment in patients with hematologic malignancies or kidney cancer who are undergoing allogeneic stem cell transplantation. * Determine the safety of this nonmyeloablative transplantation regimen in these patients. * Determine the risk of graft-versus-host-disease in patients treated with this regimen. * Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in patients treated with this regimen. * Determine the effect of lower doses of daily fludarabine on treatment-related mortality (TRM) OUTLINE: Patients are stratified according to risk (standard vs high). * Preparative regimen\*: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)\*\* IV every 12 hours on days -6 to -4. Patients who receive ATG\* include the following: * Related donor recipients who have not received combination chemotherapy within the past 6 months * Unrelated donor recipients who have not received combination chemotherapy within the past 3 months * Unrelated donor recipients who have received only 1 induction course for the treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), or blastic phase chronic myelogenous leukemia (CML) NOTE: \*\*Patients who underwent prior autologous stem cell transplantation in the past year do not receive ATG. * Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo allogeneic PBSCT on day 0. * Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours beginning on day -3 and continuing until at least day 100. Patients also receive mycophenolate mofetil IV or orally twice daily on days -3 to 30. * Donor lymphocyte infusion (DLI): Patients without active GVHD but deteriorating donor chimerism may receive DLI IV over 2 hours. After completion of study treatment, patients are followed periodically for 2 years. PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Age
0 - 75 years
Sex
ALL
Healthy Volunteers
No
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Start Date
March 26, 2002
Primary Completion Date
May 8, 2019
Completion Date
May 8, 2019
Last Updated
May 12, 2020
342
ACTUAL participants
anti-thymocyte globulin
BIOLOGICAL
cyclophosphamide
DRUG
cyclosporine
DRUG
fludarabine
DRUG
mycophenolate mofetil
DRUG
stem cell transplantation
PROCEDURE
total body irradiation
RADIATION
filgrastim
DRUG
Lead Sponsor
Masonic Cancer Center, University of Minnesota
NCT00106925
NCT05139017
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