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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 试验地点
- 30
研究概览
简要总结
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.
详细描述
OBJECTIVES:
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •See Disease Characteristics
- •Performance status:
- •Karnofsky 70-100%
- •Life expectancy:
- •At least 12 weeks
- •Hematopoietic:
- •See Disease Characteristics
- •Bilirubin less than 2.5 times upper limit of normal (ULN)
- •SGOT or SGPT less than 2.5 times ULN
- •Creatinine no greater than 1.5 mg/dL
- •Cardiovascular:
- •LVEF greater than 50% without medication
- •DLCO and FVC at least 50% predicted
- •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:
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排除标准
- 未提供