Busulfan, Fludarabine, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
This trial is active, not recruiting.
|Conditions||chronic myeloproliferative disorders, leukemia, lymphoma, multiple myeloma and plasma cell neoplasm, myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasms, precancerous condition|
|Treatments||therapeutic allogeneic lymphocytes, busulfan, cyclosporine, fludarabine phosphate, mycophenolate mofetil, peripheral blood stem cell transplantation, total body irradiation (tbi), granulocyte colony-stimulating factor (g-csf), phenytoin, methotrexate|
|Phase||phase 1/phase 2|
|Sponsor||OHSU Knight Cancer Institute|
|Collaborator||National Cancer Institute (NCI)|
|Start date||June 2005|
|End date||March 2015|
|Trial size||225 participants|
|Trial identifier||NCT00245037, CDR0000447204, OHSU-210, OHSU-HEM-05011-L, P30CA016058|
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving busulfan and fludarabine together with total-body irradiation and to see how well they work in treating patients who are undergoing a donor stem cell transplant for hematologic cancer.
|Intervention model||single group assignment|
time frame: 5 years
time frame: 5 years
Male or female participants from 18 years up to 80 years old.
DISEASE CHARACTERISTICS: - Diagnosis of a hematologic malignancy of 1 of the following high-risk types: - Acute lymphoblastic leukemia - Acute myeloid leukemia - Chronic myelogenous leukemia - Chronic lymphocytic leukemia - Myelodysplastic syndromes - Myeloproliferative disorder - Multiple myeloma - Plasma cell dyscrasias - Non-Hodgkin lymphoma - Hodgkin disease PATIENT CHARACTERISTICS: Performance status - Karnofsky 50-100% Life expectancy - Not specified Hematopoietic - Not specified Hepatic - No liver failure - No cirrhosis with evidence of portal hypertension - No alcoholic hepatitis - No esophageal varices - No chronic hepatitis - No other liver disease Renal - Not specified Cardiovascular - Left Ventricular Ejection Fraction (LVEF) > 35% - No symptomatic coronary artery disease or cardiac failure requiring therapy Pulmonary - Diffusing capacity of lung for carbon monoxide (DLCO) > 30% - Total lung capacity > 30% - Forced expiratory volume in 1 second (FEV_1) > 30% - No supplementary continuous oxygen Other - HIV negative - No active nonhematologic malignancy except localized skin cancer - No overt organ dysfunction PRIOR CONCURRENT THERAPY: - Not specified
|Official title||A Phase I/II Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of Patients With Hematologic Malignancies Using Busulfan, Fludarabine and Total Body Irradiation|
|Description||OBJECTIVES: Primary - To assess safety and toxicity of the addition of busulfan added to an established fludarabine and low-dose total-body irradiation (TBI) conditioning regimen for non-myeloablative allogeneic transplantation in patients with hematologic malignancies. (Phase I) - To assess the non-relapse mortality 1-year after conditioning with busulfan and fludarabine/TBI in patients with hematologic malignancies at moderate to high risk for graft rejection and/or relapse of underlying disease. (Phase II) Secondary - To assess overall survival 1-year survival. (Phase II) - To assess the incidence of graft rejection. (Phase II) - To assess the incidence of grade II-IV acute graft-vs-host disease (GVHD) and chronic extensive GVHD. (Phase II) - To assess rates of disease progression and/or relapse-related mortality. (Phase II) - To determine non-hematologic grade III-IV organ specific toxicity. (Phase II) OUTLINE: - Nonmyeloablative-conditioning regimen: Patients receive busulfan IV on day -5 and fludarabine IV over 30 minutes on days -4 to -2. Patients undergo total body irradiation on day 0. - Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo donor PBSC infusion on day 0. - Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180. Patients with a related stem cell donor receive oral mycophenolate mofetil twice daily on days 0-28. Patients with an unrelated stem cell donor receive oral mycophenolate mofetil 3 times daily on days 0-28 followed by a taper twice daily to day 56. Patients with evidence of relapse or persistent disease may also receive up to 3 donor lymphocyte infusions. PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study; 25 patients accrued into the Phase I and 200 patients into Phase II.|
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