Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia MT2002-02
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing Graft Failure
研究概览
简要总结
RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for patients with high risk Fanconi's anemia.
PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.
详细描述
OBJECTIVES:
Primary
- Determine whether the incidence of neutrophil engraftment is acceptable in high-risk patients with Fanconi's anemia treated with busulfan, cyclophosphamide, fludarabine, and antithymocyte globulin followed by allogeneic hematopoietic stem cell transplantation.
Secondary
- Determine the tolerability of mycophenolate mofetil in these patients.
- Determine the incidence of acute and chronic graft-vs-host disease in patients treated with this regimen.
- Determine the incidence of major infections in patients with a history of major infections treated with this regimen.
- Determine the incidence of relapse in patients with refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or acute myeloid leukemia treated with this regimen
- Determine the probability of 1-year survival of patients treated with this regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 44 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be <45 years of age with a diagnosis of Fanconi anemia with:
- •Biallelic BRCA2 mutations, or
- •Aplastic anemia, or advanced myelodysplastic syndrome (MDS) (MDS with ≥5% blasts), or acute leukemia who are ineligible for total body irradiation. Aplastic anemia is defined as having at least one of the following (with or without cytogenetic abnormalities): platelet count <20 * 10^9, - absolute neutrophil count (ANC) <5 * 10^8/L, - Hgb <8 g/dL
- •Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors will be typed for HLA-A and B using serological level typing and for DRB1 using high resolution molecular typing.
- •Adequate major organ function including:
- •Cardiac: ejection fraction >45%
- •Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites, no cirrhosis)
- •Karnofsky performance status >70% or Lansky >50%
- •Women of child bearing potential must be using adequate birth control and have a negative pregnancy test.
排除标准
- •Active CNS leukemia at time of HSCT.
- •Active uncontrolled infection within one week of hematopoietic stem cell transplant (HSCT).
- •Pregnant or lactating female.
- •Donor Inclusion Criteria:
- •Donor must be in good health based on review of systems and results of physical examination.
- •Donor must have a normal hemoglobin, white count, platelet count and partial thromboplastin time (PTT), and a negative diepoxybutane (DEB) test.
- •HIV-NAT negative, HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
- •Female donors of childbearing potential must have a negative pregnancy test.
- •Unrelated donors must agree to peripheral blood stem cell (PBSC) donation
- •Donor Exclusion Criteria:
- •Donor is a lactating female.
研究组 & 干预措施
Marrow Isolex
Bone marrow processed using Isolex300i
干预措施: cyclophosphamide (Drug)
Marrow Isolex
Bone marrow processed using Isolex300i
干预措施: anti-thymocyte globulin (Biological)
Marrow Isolex
Bone marrow processed using Isolex300i
干预措施: filgrastim (Biological)
Marrow Isolex
Bone marrow processed using Isolex300i
干预措施: busulfan (Drug)
Marrow Isolex
Bone marrow processed using Isolex300i
干预措施: fludarabine phosphate (Drug)
Marrow Isolex
Bone marrow processed using Isolex300i
干预措施: methylprednisolone (Drug)
Marrow Isolex
Bone marrow processed using Isolex300i
干预措施: Hematopoietic stem cell transplantation (Biological)
USB arm
No processing
干预措施: anti-thymocyte globulin (Biological)
USB arm
No processing
干预措施: filgrastim (Biological)
USB arm
No processing
干预措施: busulfan (Drug)
USB arm
No processing
干预措施: cyclophosphamide (Drug)
USB arm
No processing
干预措施: fludarabine phosphate (Drug)
USB arm
No processing
干预措施: methylprednisolone (Drug)
USB arm
No processing
干预措施: Hematopoietic stem cell transplantation (Biological)
Marrow Clinimacs
Bone marrow processed using CliniMACS system
干预措施: anti-thymocyte globulin (Biological)
Marrow Clinimacs
Bone marrow processed using CliniMACS system
干预措施: filgrastim (Biological)
Marrow Clinimacs
Bone marrow processed using CliniMACS system
干预措施: busulfan (Drug)
Marrow Clinimacs
Bone marrow processed using CliniMACS system
干预措施: cyclophosphamide (Drug)
Marrow Clinimacs
Bone marrow processed using CliniMACS system
干预措施: fludarabine phosphate (Drug)
Marrow Clinimacs
Bone marrow processed using CliniMACS system
干预措施: methylprednisolone (Drug)
Marrow Clinimacs
Bone marrow processed using CliniMACS system
干预措施: Hematopoietic stem cell transplantation (Biological)
Sibling without CliniMacs
Sibling donor without the use of CliniMACS system
干预措施: anti-thymocyte globulin (Biological)
Sibling without CliniMacs
Sibling donor without the use of CliniMACS system
干预措施: filgrastim (Biological)
Sibling without CliniMacs
Sibling donor without the use of CliniMACS system
干预措施: busulfan (Drug)
Sibling without CliniMacs
Sibling donor without the use of CliniMACS system
干预措施: cyclophosphamide (Drug)
Sibling without CliniMacs
Sibling donor without the use of CliniMACS system
干预措施: fludarabine phosphate (Drug)
Sibling without CliniMacs
Sibling donor without the use of CliniMACS system
干预措施: methylprednisolone (Drug)
Sibling without CliniMacs
Sibling donor without the use of CliniMACS system
干预措施: Hematopoietic stem cell transplantation (Biological)
结局指标
主要结局
Number of Participants Experiencing Graft Failure
时间窗: Day 30
Graft failure is defined as absolute neutrophil count( ANC ) \<5 x 10\^8/L by day 30.
次要结局
- Number of Participants Experiencing Acute Graft-Versus-Host Disease(Day 42)
- Number of Participants Experiencing Relapse(1 Year)
- Number of Participants Experiencing Overall Survival(1 Year)
- Number of Participants Experiencing Major Infections(Day 1 through 1 year post-transplant)
- Number of Participants Experiencing Chronic Graft-Versus-Host Disease(1 year)