Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Selected Non-Malignant Diseases
Overview
- Phase
- Phase 2
- Intervention
- Fludarabine
- Conditions
- Bone Marrow Failure
- Sponsor
- Columbia University
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Number of participants with Adverse Events
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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)
Intervention: Fludarabine
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)
Intervention: Busulfan
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)
Intervention: Alemtuzumab
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)
Intervention: Fludarabine
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)
Intervention: Cyclophosphamide
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)
Intervention: Rabbit Anti-thymocyte Globulin
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
Intervention: Fludarabine
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
Intervention: Cyclophosphamide
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
Intervention: Horse Anti-thymocyte Globulin
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
Intervention: Fludarabine
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
Intervention: Cyclophosphamide
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
Intervention: Rabbit Anti-thymocyte Globulin
Outcomes
Primary Outcomes
Number of participants with Adverse Events
Time Frame: 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)
Secondary Outcomes
- 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)