A Study of Thymic Shielding in Recipients of Total Body Irradiation, Cyclophosphamide, and Fludarabine Followed by Alternate Donor Hematopoietic Stem Cell Transplantation in Patients With Fanconi Anemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment
研究概览
简要总结
The purpose of this study is to determine whether thymic shielding during total body irradiation can be given and whether it will reduce the risk of infections in Fanconi Anemia patients undergoing alternate donor (not a matched sibling) stem cell transplants.
详细描述
All subjects will be given the same treatment regimen of total body irradiation (TBI), Fludarabine, Cyclophosphamide, and anti-thymocyte globulin (ATG), followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding.
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
- 1 Day 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be less than (<) 18 years of age with a diagnosis of Fanconi anemia.
- •Patients must have an HLA-A, B, DRB1 identical unrelated donor or less than or equal to (≤)1 antigen mismatched related (non-HLA-matched sibling) or <1 antigen mismatched unrelated UCB donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing.
- •Patients with FA must have aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below.
- •Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions
- •Platelet count <20 x 10^9/L
- •ANC <5 x 10^8/L
- •Hgb <8 g/dL
- •Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies
- •High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)
- •Adequate major organ function including
- •Cardiac: ejection fraction greater than (>)45%
- •Hepatic: bilirubin, AST/ALT, ALP <2 x normal
- •Karnofsky performance status >70% or Lansky performance status >50%
- •Women of child-bearing age must be using adequate birth control and have a negative pregnancy test
排除标准
- •Available HLA-genotypically identical related donor
- •History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies)
- •Refractory anemia with excess blasts, or leukemia
- •Active central nervous system (CNS) leukemia at time of hematopoietic cell transplant (HCT)
- •History of squamous cell carcinoma of the head/neck/cervix within 2 years of HCT
- •Pregnant or lactating female
- •Prior radiation therapy preventing use of total body irradiation (TBI) 450 centigray (cGy)
研究组 & 干预措施
HSCT Patients
Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
干预措施: Hematopoietic Stem Cell Transplant (Procedure)
HSCT Patients
Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
干预措施: Thymic Shielding During Radiation (Procedure)
HSCT Patients
Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
干预措施: Total Body Irradiation (Procedure)
HSCT Patients
Patients who received total body irradiation (450 cGy [centigray]) with thymic shielding prior to chemotherapy regimen and Hematopoietic Stem Cell Transplant (HSCT)
干预措施: Cyclophosphamide, Fludarabine (Drug)
结局指标
主要结局
Number of Patients Who Exhibited Hematopoietic Recovery and Engraftment
时间窗: Day 42 after hematopoietic cell transplant
Calculated from Day 1 of hematopoietic cell transplant to Day 42 post-transplant. Hematopoietic recovery and engraftment is defined as the first of three consecutive days the patient's absolute neutrophil count is greater than or equal to 0.5X10\^9/Liter.
次要结局
- Number of Patients Who Exhibited Secondary Graft Failure(Day 100 after hematopoietic cell transplant)
- Number of Patients With Acute Graft Versus-Host Disease (aGVHD)(Day 100 after hematopoietic cell transplant)
- Number of Patients With Chronic Graft Versus-Host Disease (GVHD)(1 year after hematopoietic cell transplant)
- Number of Patients Who Exhibited Regimen-related Toxicity (RRT)(1 year after hematopoietic cell transplant)
- Immune Reconstitution - Mean Value (1 Year)(1 year post-transplant.)
- Immune Reconstitution - Mean Value (2 Years)(at 2 years after transplant)
- Number of Patients Alive at 1 Year(1 year after transplant)
- Number of Patients Alive at 2 Years(2 years after transplant)