Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed By Donor Bone Marrow Transplant in Treating Patients With Sickle Cell Anemia and Other Blood Disorders
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving sirolimus and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by a donor bone marrow transplant works in treating patients with sickle cell anemia and other blood disorders.
Sickle Cell Disease
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: Allogeneic bone marrow transplantation
Radiation: total-body irradiation
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched and HLA-Matched Bone Marrow for Patients With Sickle Cell Anemia and Other Hemoglobinopathies|
- Transplant-related mortality at day 100 and 1 year after bone marrow transplantation (BMT) [ Time Frame: 1 year after bone marrow transplant ] [ Designated as safety issue: No ]
- Risk-stratified estimates of 2-year progression-free survival [ Time Frame: 2 years from bone marrow transplant ] [ Designated as safety issue: No ]
- Time to recovery of circulating neutrophils and platelets after chemotherapy [ Time Frame: 60 days from bone marrow transplant ] [ Designated as safety issue: No ]
- Donor chimerism at 30, 60, 180, and 365 days after bone marrow transplant [ Time Frame: 1 year from bone marrow transplant ] [ Designated as safety issue: No ]
- Development of graft-vs-host disease [ Time Frame: 1 year from bone marrow transplant ] [ Designated as safety issue: No ]
|Study Start Date:||May 2007|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
- Determine the transplant-related mortality and progression-free survival of patients with severe hemoglobinopathies receiving nonmyeloablative conditioning comprising fludarabine phosphate, cyclophosphamide, and total-body irradiation followed by partially HLA-mismatched bone marrow transplantation from first-degree relatives or HLA-matched donors.
- Characterize donor hematopoietic chimerism at 30, 60, and 180 days after transplantation in these patients.
- Determine the hematologic and non-hematologic toxicity of this regimen in these patients.
- Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients also undergo total-body irradiation on day -1.
- Bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Donors receive filgrastim (G-CSF) subcutaneously beginning on day -5 to day -1.
- Graft-versus-host disease prophylaxis: Patients receive sirolimus orally daily on days 5-365 and oral mycophenolate mofetil 3 times a day on days 5-35.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00489281
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Recruiting|
|Baltimore, Maryland, United States, 21231-2410|
|Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 firstname.lastname@example.org|
|Study Chair:||Javier Bolanos-Meade, MD||Sidney Kimmel Comprehensive Cancer Center|