Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Incidence of Neutrophil Engraftment
研究概览
简要总结
Fludarabine-based preparative regimen followed by an allogeneic hematopoietic stem cell transplant using related or unrelated donor in persons 0-70 years of age diagnosed with dyskeratosis congenita or severe aplastic anemia who have bone marrow failure characterized by a requirement for red blood cell and platelet transfusions. Three different preparative regimens are included based on disease and donor type.
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
- 0 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 0 - 70 years
- •Acceptable hematopoeitic stem cell donor
- •Dyskeratosis Congenita (DC) with evidence of BM failure defined as:
- •requirement for red blood cell and/or platelet transfusions or
- •requirement for G-CSF or GM-CSF or erythropoietin or
- •refractory cytopenias having one of the following three
- •platelets <50,000/uL or transfusion dependent
- •absolute neutrophil count <500/uL without hematopoietic growth factor support
- •hemoglobin <9g/uL or transfusion dependent
- •Diagnosis of DC with a triad of mucocutaneous features:
- •oral leukoplakia
- •nail dystrophy
- •abnormal reticular skin hyperpigmentation, or
- •Diagnosis of DC with one of the following:
- •short telomeres (under a research study)
- •mutation in telomerase holoenzyme (DKC1, TERT, TERC, NOP10, NHP2, TCAB1)
- •mutation in shelterin complex (TINF2)
- •mutation in telomere-capping complex (CTC1)
- •Severe Aplastic Anemia (SAA) primary transplant with evidence of BM failure:
- •Refractory cytopenia defined by bone marrow cellularity <50% (with < 30% residual hematopoietic cells)
- •Diagnosis of SAA with refractory cytopenias having one of the following three:
- •platelets <20,000/uL or transfusion dependent
- •absolute neutrophil count <500/uL without hematopoietic growth factor support
- •absolute reticulocyte count <20,000/uL
- •Severe Aplastic Anemia (SAA) requiring a 2nd transplant
- •Graft failure as defined by blood/marrow chimerism of < 5%
- •Early myelodysplastic features
- •With or without clonal cytogenetic abnormalities
- •Adequate organ function defined as:
- •cardiac: left ventricular ejection fraction ≥ 35% with no evidence of decompensated heart failure
- •pulmonary: DLCO ≥30% predicted, no supplemental oxygen requirement
- •renal: Glomerular filtration rate (GFR) ≥30% predicted
- •Voluntary written consent
排除标准
- •Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
- •Pregnant or lactating
- •Uncontrolled infection
- •Prior radiation therapy (applies to SAA patients only)
- •Diagnosis of Fanconi anemia based on DEB
- •Diagnosis of dyskeratosis congenita with advanced MDS or acute myeloid leukemia with >30% blasts
研究组 & 干预措施
Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Alemtuzumab (Drug)
Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Fludarabine (Drug)
Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Cyclophosphamide (Drug)
Arm A Dyskeratosis Congenita (DKC) (non-haploidentical donor)
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Stem Cell Transplant (Biological)
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Alemtuzumab (Drug)
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Fludarabine (Drug)
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Cyclophosphamide (Drug)
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Total Body Irradiation (Radiation)
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Stem Cell Transplant (Biological)
Arm B: Severe Aplastic Anemia (SAA ) (non-matched related, non-haploidentical donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Anti-thymocyte globulin (Drug)
Arm C: Severe Aplastic Anemia (matched related donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Alemtuzumab (Drug)
Arm C: Severe Aplastic Anemia (matched related donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Fludarabine (Drug)
Arm C: Severe Aplastic Anemia (matched related donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Cyclophosphamide (Drug)
Arm C: Severe Aplastic Anemia (matched related donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Total Body Irradiation (Radiation)
Arm C: Severe Aplastic Anemia (matched related donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Stem Cell Transplant (Biological)
Arm C: Severe Aplastic Anemia (matched related donor)
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Anti-thymocyte globulin (Drug)
Arm D: Dyskeratosis Congenita (DKC), PTCy platform
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Alemtuzumab (Drug)
Arm D: Dyskeratosis Congenita (DKC), PTCy platform
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Fludarabine (Drug)
Arm D: Dyskeratosis Congenita (DKC), PTCy platform
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Cyclophosphamide (Drug)
Arm D: Dyskeratosis Congenita (DKC), PTCy platform
Fludarabine based preparative regimen, including alemtuzumab, cyclophosphamide, fludarabine, followed by stem cell transplant for the treatment of dyskeratosis congenita.
干预措施: Stem Cell Transplant (Biological)
Arm E: Severe Aplastic Anemia (SAA), PTCy platform
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Alemtuzumab (Drug)
Arm E: Severe Aplastic Anemia (SAA), PTCy platform
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Fludarabine (Drug)
Arm E: Severe Aplastic Anemia (SAA), PTCy platform
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Cyclophosphamide (Drug)
Arm E: Severe Aplastic Anemia (SAA), PTCy platform
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Total Body Irradiation (Radiation)
Arm E: Severe Aplastic Anemia (SAA), PTCy platform
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Stem Cell Transplant (Biological)
Arm E: Severe Aplastic Anemia (SAA), PTCy platform
Fludarabine based preparative regimen which includes: cyclophosphamide, fludarabine, rabbit ATG and total body irradiation. Followed by stem cell transplant.
干预措施: Anti-thymocyte globulin (Drug)
结局指标
主要结局
Incidence of Neutrophil Engraftment
时间窗: Day 42
Incidence of neutrophil engraftment by day 42.
Incidence of Platelet Engraftment
时间窗: 1 year
Incidence of platelet engraftment at 1 year
次要结局
- Incidence of Regimen Related Mortality(Day 100)
- Incidence of Acute Graft-versus-host Disease(Day 100)
- Incidence of Chronic Graft-versus-host Disease(1 Year)
- Incidence of Secondary Malignancies(1 Year)