Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
- Conditions
- Bone Marrow FailureOsteopetrosisFanconi AnemiaSevere Combined Immunodeficiency
- Interventions
- Registration Number
- NCT01019876
- Lead Sponsor
- Columbia University
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regimen A - Standard Conditioning Regimen Fludarabine 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) Regimen A - Standard Conditioning Regimen Busulfan 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) Regimen A - Standard Conditioning Regimen Alemtuzumab 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) Regimen B Fludarabine 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) Regimen B Cyclophosphamide 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) Regimen B Rabbit Anti-thymocyte Globulin 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) Regimen C Fludarabine 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 Regimen C Cyclophosphamide 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 Regimen D Fludarabine 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 Regimen D Cyclophosphamide 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 Regimen D Rabbit Anti-thymocyte Globulin 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 Regimen C Horse Anti-thymocyte Globulin 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
- Primary Outcome Measures
Name Time Method Number of participants with Adverse Events 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 Outcome Measures
Name Time Method Risk of disease progression Up to 1 year To determine the risk of disease progression (including neuropsychological deterioration in patients with metabolic non-malignant diseases) following a Flu/CY or Bu/Flu based conditioning regimen.
Immune reconstitution Up to 1 year Titers of immune cells (T cells, B cells, and NK cells) from peripheral blood will be measured following a Flu/CY or Bu/Flu based conditioning regimen and AlloSCT in patients with selected non-malignant diseases.
Incidence of graft versus host disease (GVHD) Up to 1 year Incidence of GVHD in participants following a Flu/Cy or Bu/Flu based conditioning regimen.
Metabolic/Immune reconstitution Up to 1 year To determine metabolic/immune (gene/protein) reconstitution by standard biochemical/PCR assays in patients.
Trial Locations
- Locations (1)
Columbia University Medical Center
🇺🇸New York, New York, United States