A Phase II Trial of Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Unrelated Donors in Patients With Advanced Hematologic Malignancies and Hematological Disorders
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 260
- 主要终点
- Neutrophil Engraftment - The Days Till ANC Recovery
研究概览
简要总结
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem 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 tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil, and sirolimus before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well donor peripheral stem cell transplant works in treating patients with advanced hematologic cancer or other disorders.
详细描述
OBJECTIVES:
Primary
- To evaluate hematopoietic recovery, using neutrophil and platelet engraftment as the primary criterion, in patients with advanced hematologic malignancies or other disorders undergoing allogeneic peripheral blood stem cell (PBSC) transplantation from matched unrelated donors.
- To evaluate the incidence of acute and chronic graft-versus-host-disease (GVHD) in patients undergoing allogeneic PBSC transplantation from matched unrelated donors.
Secondary
- To evaluate the impact of HLA class I and class II allele-matching on the incidence of GVHD and on the survival outcome of these patients.
- To evaluate overall survival, disease-free survival, and relapse in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 120 Years（Child, Adult, Older 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 lymphocytic leukemia (ALL), meeting one of the following criteria:
- •In first relapse or beyond
- •High-risk ALL, defined by any of the following:
- •Hypoploidy (≤ 44 chromosomes)
- •Pseudodiploidy with translocations or molecular evidence of t(9;22), 11q23, or t(8;14), excluding B-cell ALL
- •Elevated WBC at presentation (WBC > 20,000/mm³ [for patients > 18 years of age]; WBC > 200,000/mm³ [for patients 12-18 years of age])
- •Acute myeloid leukemia (AML), meeting one of the following criteria:
- •In first complete remission
- •Failed to achieve remission
- •In first relapse or beyond
- •Secondary AML (> 30% blasts in marrow aspirate)
- •Should receive induction chemotherapy to obtain remission, if possible, before transplant
- •Chronic myelogenous leukemia, meeting one of the following criteria:
- •In first or second chronic phase or accelerated phase
- •In blast crisis, defined as > 30% promyelocytes plus blasts in the bone marrow
- •Myelodysplastic syndromes, including any of the following:
- •Refractory anemia with excess blasts (RAEB)
- •Chronic myelomonocytic leukemia
- •RAEB in transformation
- •Refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, or multiple myeloma
- •Received and failed front-line therapy, high-dose therapy and autologous stem cell transplantation, or salvage therapy
- •Myeloproliferative disorders/myelofibrosis may be allowed on a case by case basis
- •Severe aplastic anemia, paroxysmal nocturnal hemoglobinuria, or any other hematologic disorder requiring transplantation
- •Patients > 55 years of age with hematologic diseases treatable by allogeneic stem cell transplantation who are not eligible for IRB 99190 are eligible
- •No uncontrolled CNS involvement of disease
- •No matched (6/6) related donor available
- •HLA-identical unrelated donor available
- •HLA-phenotypically identical for HLA-A and HLA-B alleles and identical for DRB1 alleles by DNA typing for both class I and class II antigens
- •Allele mismatch for HLA class I (i.e., B 2701 vs B 2702) allowed if no alternative donors
- •Allele mismatch for class II (i.e., DRB1 0401 vs 0402) or minor mismatch for class I cross reactive group (CREG) (i.e., A 2 vs A 28) allowed in patients ≤ 35 years of age requiring urgent transplant
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status 50-100%
- •Life expectancy > 8 weeks
- •LVEF ≥ 45% at rest
- •AST ≤ 2 times normal (unless liver function abnormality is due to underlying disease)
- •Total bilirubin < 1.5 times normal (unless liver function abnormality is due to underlying disease)
- •Creatinine ≤ 1.5 times normal OR creatinine clearance ≥ 60 mL/min
- •DLCO ≥ 40% of predicted (corrected for hemoglobin)
- •No coexisting medical problem that would significantly increase the risk of the transplant procedure
- •HIV negative
- •Not pregnant
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
排除标准
- 未提供
研究组 & 干预措施
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: mycophenolate mofetil (Drug)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: cyclophosphamide (Drug)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: sirolimus (Drug)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: methotrexate (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: melphalan (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: cyclosporine (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: mycophenolate mofetil (Drug)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: cyclosporine (Drug)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: tacrolimus (Drug)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: busulfan (Drug)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: cyclosporine (Drug)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: tacrolimus (Drug)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: fludarabine phosphate (Drug)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: total-body irradiation (Radiation)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: peripheral blood stem cell transplantation (Procedure)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: methotrexate (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: peripheral blood stem cell transplantation (Procedure)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: peripheral blood stem cell transplantation (Procedure)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: peripheral blood stem cell transplantation (Procedure)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: total-body irradiation (Radiation)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: peripheral blood stem cell transplantation (Procedure)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: peripheral blood stem cell transplantation (Procedure)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: total-body irradiation (Radiation)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: mycophenolate mofetil (Drug)
Regimen VI
Patients receive busulfan IV over 3 hours and fludarabine phosphate IV over 30 minutes on days -5 to -2.
干预措施: sirolimus (Drug)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: cyclosporine (Drug)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: methotrexate (Drug)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: sirolimus (Drug)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: tacrolimus (Drug)
Regimen I
Patients undergo total body irradiation (TBI) on days -7 to -4 and receive cyclophosphamide IV on days -3 and -2. Alternatively, patients may receive cyclophosphamide on days -7 and -6 and undergo TBI on days -4 to -1.
干预措施: mycophenolate mofetil (Drug)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: busulfan (Drug)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: cyclosporine (Drug)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: cyclophosphamide (Drug)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: mycophenolate mofetil (Drug)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: etoposide (Drug)
Regimen II
Patients receive busulfan IV over 2 hours once on day -8 and then every 6 hours on days -7 to -4. Patients also receive cyclophosphamide IV on days -3 and -2.
干预措施: tacrolimus (Drug)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: cyclosporine (Drug)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: methotrexate (Drug)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: sirolimus (Drug)
Regimen III
Patients undergo TBI on days -7 to -4 and receive etoposide IV on day -3.
干预措施: tacrolimus (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: fludarabine phosphate (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: methotrexate (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: tacrolimus (Drug)
Regimen IV
Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and melphalan IV on day -2.
干预措施: sirolimus (Drug)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: methotrexate (Drug)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: mycophenolate mofetil (Drug)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: fludarabine phosphate (Drug)
Regimen V
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
干预措施: sirolimus (Drug)
结局指标
主要结局
Neutrophil Engraftment - The Days Till ANC Recovery
时间窗: Up to 180 days post transplant
The primary engraftment endpoint, neutrophil engraftment, is defined as the first of three consecutive days on which the absolute neutrophil count is \> 500/µL. The duration and extent of neutrophil engraftment is the time from transplant to neutrophil engraftment.
次要结局
- Two-year Overall Survival(Up to 2 years post transplant)