Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Number of participants with Adverse Events
研究概览
简要总结
This study proposes the use of a reduced intensity chemotherapy/radiation therapy regimen followed by stem cell transplantation, as compared to standard ablative chemotherapy regimens associated with stem cell transplantation, in a population of patients with non-malignant diseases (non-cancer). Eligible patients will have a non-malignant disease in one of the following four strata: bone marrow failure syndromes, immunodeficiencies, inborn errors of metabolism, or histiocytoses. Patients will be assigned to therapy according to diagnosis. Patients will be stratified by disease into one of four strata and treatment regimens will be based on specific disease criteria and conditions. Although these diseases are non-malignant in name, they are often malignant by nature of the disease progression, treatment and associated complications.
详细描述
This treatment program proposes the use of a reduced intensity chemotherapy regimen, which has been shown to be effective for inducing remission and cure in these diseases. Studies have shown that the use of non-myeloablative chemotherapy regimens have resulted in 75-100% engraftment (replacement of the recipient bone marrow with the donor bone marrow), and significantly reduced transplant related complications as compared to the standard myeloablative chemotherapy regimens.
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
- — 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Regimen A - Standard Conditioning Regimen
Standard conditioning regimen for all diseases except those diseases or conditions noted in Regimen B, C and D:
- Fludarabine (180 mg/m2 total dose)
- Busulfan (16 mg/kg less than or equal to 4 yrs and 12.8 mg/ kg >4 yrs total dose)
- Alemtuzumab (2mg/m2 x 1day, 6mg/m2 x 2 days, 20mg/m2 x 2days)
干预措施: Fludarabine (Drug)
Regimen A - Standard Conditioning Regimen
Standard conditioning regimen for all diseases except those diseases or conditions noted in Regimen B, C and D:
- Fludarabine (180 mg/m2 total dose)
- Busulfan (16 mg/kg less than or equal to 4 yrs and 12.8 mg/ kg >4 yrs total dose)
- Alemtuzumab (2mg/m2 x 1day, 6mg/m2 x 2 days, 20mg/m2 x 2days)
干预措施: Busulfan (Drug)
Regimen A - Standard Conditioning Regimen
Standard conditioning regimen for all diseases except those diseases or conditions noted in Regimen B, C and D:
- Fludarabine (180 mg/m2 total dose)
- Busulfan (16 mg/kg less than or equal to 4 yrs and 12.8 mg/ kg >4 yrs total dose)
- Alemtuzumab (2mg/m2 x 1day, 6mg/m2 x 2 days, 20mg/m2 x 2days)
干预措施: Alemtuzumab (Drug)
Regimen B
Includes patients with a diagnosis of: Osteopetrosis and Severe Aplastic Anemia with a history of >10 blood transfusions, or Blackfan-Diamond's anemia, or Chronic Granulomatous Disease, or Wiskott Aldrich Syndrome:
- Cyclophosphamide (200 mg/kg total dose)
- Fludabarine (180 mg/m2 total dose)
- Rabbit Anti-thymocyte Globulin (8mg/kg total dose)
干预措施: Fludarabine (Drug)
Regimen B
Includes patients with a diagnosis of: Osteopetrosis and Severe Aplastic Anemia with a history of >10 blood transfusions, or Blackfan-Diamond's anemia, or Chronic Granulomatous Disease, or Wiskott Aldrich Syndrome:
- Cyclophosphamide (200 mg/kg total dose)
- Fludabarine (180 mg/m2 total dose)
- Rabbit Anti-thymocyte Globulin (8mg/kg total dose)
干预措施: Cyclophosphamide (Drug)
Regimen B
Includes patients with a diagnosis of: Osteopetrosis and Severe Aplastic Anemia with a history of >10 blood transfusions, or Blackfan-Diamond's anemia, or Chronic Granulomatous Disease, or Wiskott Aldrich Syndrome:
- Cyclophosphamide (200 mg/kg total dose)
- Fludabarine (180 mg/m2 total dose)
- Rabbit Anti-thymocyte Globulin (8mg/kg total dose)
干预措施: Rabbit Anti-thymocyte Globulin (Drug)
Regimen C
Includes patients with any one of the following specific diagnosis: Fanconi Anemia, Dyskeratosis Congenita or Schwachman Diamond Syndrome
- Cyclophosphamide (40 mg/kg total dose)
- Fludarabine (140 mg/m2 total dose)
- Anti-Thymocyte Globulin (horse) (150mg/kg total dose)/TBI 450 cGy
干预措施: Fludarabine (Drug)
Regimen C
Includes patients with any one of the following specific diagnosis: Fanconi Anemia, Dyskeratosis Congenita or Schwachman Diamond Syndrome
- Cyclophosphamide (40 mg/kg total dose)
- Fludarabine (140 mg/m2 total dose)
- Anti-Thymocyte Globulin (horse) (150mg/kg total dose)/TBI 450 cGy
干预措施: Cyclophosphamide (Drug)
Regimen C
Includes patients with any one of the following specific diagnosis: Fanconi Anemia, Dyskeratosis Congenita or Schwachman Diamond Syndrome
- Cyclophosphamide (40 mg/kg total dose)
- Fludarabine (140 mg/m2 total dose)
- Anti-Thymocyte Globulin (horse) (150mg/kg total dose)/TBI 450 cGy
干预措施: Horse Anti-thymocyte Globulin (Drug)
Regimen D
Includes patients with the following specific diagnosis of: Severe Combined Immune Deficiency Syndrome with no evidence of host NK function (will receive Regimen A) and matched related donor
- Cyclophosphamide (30 mg/kg total dose)
- Fludarabine (90 mg/m2 total dose)
- Rabbit anti-thymocyte globulin (Thymoglobulin)(TMG)**(8 mg/kg total dose)
TMG only in family haploidentical and unrelated donors
干预措施: Fludarabine (Drug)
Regimen D
Includes patients with the following specific diagnosis of: Severe Combined Immune Deficiency Syndrome with no evidence of host NK function (will receive Regimen A) and matched related donor
- Cyclophosphamide (30 mg/kg total dose)
- Fludarabine (90 mg/m2 total dose)
- Rabbit anti-thymocyte globulin (Thymoglobulin)(TMG)**(8 mg/kg total dose)
TMG only in family haploidentical and unrelated donors
干预措施: Cyclophosphamide (Drug)
Regimen D
Includes patients with the following specific diagnosis of: Severe Combined Immune Deficiency Syndrome with no evidence of host NK function (will receive Regimen A) and matched related donor
- Cyclophosphamide (30 mg/kg total dose)
- Fludarabine (90 mg/m2 total dose)
- Rabbit anti-thymocyte globulin (Thymoglobulin)(TMG)**(8 mg/kg total dose)
TMG only in family haploidentical and unrelated donors
干预措施: Rabbit Anti-thymocyte Globulin (Drug)
结局指标
主要结局
Number of participants with Adverse Events
时间窗: Up to 2 years
The number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE - Version 4.0)
次要结局
- Risk of disease progression(Up to 1 year)
- Immune reconstitution(Up to 1 year)
- Incidence of graft versus host disease (GVHD)(Up to 1 year)
- Metabolic/Immune reconstitution(Up to 1 year)