Treatment of Bone Marrow to Prevent Graft-Versus-Host Disease in Patients With Acute or Chronic Leukemia Undergoing Bone Marrow Transplantation
A Multi-Center, Open Label, Randomized, Active Controlled Phase II/III Clinical Trial to Evaluate the Safety and Efficacy of Processed Unrelated Bone Marrow in Patients With Acute or Chronic Leukemia
PhasePhase 2/Phase 3
Lead SponsorChimeric Therapies
StatusCompleted No Results Posted
Indication/ConditionLeukemia Graft Versus Host Disease Myelodysplastic Syndromes
Intervention/Treatmentmethylprednisolone tacrolimus in vitro-treated bone marrow allogeneic hematopoietic stem cells cyclophosphamide Anti-thymocyte Globulin (Rabbit) fludarabine sargramostim ...
RATIONALE: Bone marrow that has been treated to remove certain white blood cells may reduce the chance of developing graft-versus-host disease following bone marrow transplantation.
PURPOSE: Randomized phase II/III trial to compare the effectiveness of treated bone marrow with that of untreated bone marrow in preventing graft-versus-host disease in patients with acute or chronic leukemia who are undergoing bone marrow transplantation.
Compare the efficacy of processed (cell depleted) vs unprocessed (conventional) unrelated bone marrow transplantation in reducing grade III/IV acute graft vs host disease (GVHD) in patients with acute or chronic leukemia or myelodysplastic syndromes.
Compare the safety of these regimens in these patients.
Compare the disease-free survival rate at 100 days and at 6 months in patients treated with these regimens.
Compare the time to engraftment and percent engraftment in patients treated with these regimens.
Compare the reduction rate of grade II or greater acute and chronic GVHD in patients treated with these regimens.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to degree of HLA matching and disease (chronic vs acute). Acute myelogenous leukemia patients are further stratified according to prior myelodysplastic syndromes (yes vs no). Patients are randomized to one of two bone marrow transplantation arms.
All patients receive a conditioning regimen comprising fludarabine IV on day -6, cyclophosphamide IV on days -5 and -4, anti-thymocyte globulin IV on days -4 and -2, and total body irradiation on days -3 to 0. Patients also receive methylprednisolone IV every 12 hours for 4 doses on days -2 to 0. Tacrolimus IV is administered continuously on day -1 and continues either orally or IV for 6 months. Bone marrow is infused on day 0. Filgrastim (G-CSF) is administered subcutaneously from day 0 until blood counts recover.
Arm I: Patients receive allogeneic bone marrow that has been processed to produce a mononuclear cell preparation.
Arm II: Patients receive unprocessed allogeneic bone marrow. Patients are followed weekly for 100 days and then at 6 months.
PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 17 months.
DISEASE CHARACTERISTICS: Diagnosis of one of the following: Acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL) in first early relapse, second remission, or subsequent remission AML in first complete remission with one of the following adverse features: Antecedent hematologic disorder such as myelodysplasia AML resulting from prior chemotherapy or radiotherapy More than 1 course of induction chemotherapy to achieve remission or adverse cytogenetics such as Philadelphia chromosome 9:22, +8, +11; abnormal 12p; or deletions of chromosomes 5, 7, or 20 (3:3) ALL in first complete remission with poor risk cytogenetics such as Philadelphia chromosome 9:22, 8:14, or 4:11 OR WBC greater than 100,000/mm3 OR Time to achieve complete remission more than 4 weeks Chronic myelogenous leukemia in chronic or accelerated phase Myelodysplastic syndromes Refractory anemia with excess blasts (RAEB) OR RAEB in transformation Unrelated bone marrow donor available If matched at 6 of 6 HLA-A, -B, and -DR loci, patient must be 12 to 50 years If matched at 5 of 6 loci, patient must be 12 to 35 years No matched sibling donor available No uncontrolled CNS leukemia PATIENT CHARACTERISTICS: Age: See Disease Characteristics 12 to 50 Performance status: Karnofsky 70-100% Life expectancy: At least 12 weeks Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 2.5 times upper limit of normal (ULN) SGOT or SGPT less than 2.5 times ULN Renal: Creatinine no greater than 1.5 mg/dL Cardiovascular: LVEF greater than 50% without medication Pulmonary: DLCO and FVC at least 50% predicted Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other serious medical illness No uncontrolled diabetes mellitus No uncontrolled and/or active infection HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior immunotherapy and recovered At least 1 year since prior autologous transplantation No prior allogeneic transplantation Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy (except hydroxyurea) and recovered Endocrine therapy: At least 3 weeks since prior hormonal therapy and recovered Radiotherapy: See Disease Characteristics At least 3 weeks since prior radiotherapy and recovered No prior radiotherapy at doses that would preclude study Surgery: Not specified