Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia
Anemia, Sickle Cell
Hemoglobin SC Disease
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Stem Cell Transplantation Following Nonmyeloablative Chemotherapy in Patients With Hemoglobinopathies|
- Evidence of engraftment of donor hematopoietic cells following administration of low doses of busulfan and fludarabine [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Solid organ toxicity related to the conditioning regimen [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
- Incidence of grade II, III, or IV acute graft versus host disease (GVHD) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Level of disease response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
|Study Start Date:||September 2001|
|Study Completion Date:||November 2003|
|Primary Completion Date:||November 2003 (Final data collection date for primary outcome measure)|
Experimental: Allogeneic stem cell transplantation
Participants will receive a nonmyeloablative conditioning regimen of fludarabine and busulfan prior to allogeneic peripheral blood stem cell (CD34+) infusions. FK506 and prednisone will be administered for graft versus host disease (GVHD) prophylaxis.
0.8 mg/kg/d administered as a single intravenous infusion over 3 hours for 4 days. All infusions are anticipated to be given in the outpatient clinic.
Other Name: BusulfexDrug: Fludarabine
30 mg/m^2/d administered as a bolus infusion over 30 minutes for 4 days. All infusions are anticipated to be given in the outpatient clinic.
Other Names:Drug: FK506
0.15 mg/kg taken orally daily for 12 to 14 weeks
Other Names:Drug: Prednisone
0.5 mg/kg taken orally four times daily on Day 7 and increase to 1 mg/kg taken orally four times daily on Day 14. Participants will continue regimen until Day 30 before a 20-25% taper per week.
Hemoglobinopathies, such as sickle cell disease and thalassemia major, are genetic diseases associated with significant morbidity and premature death. Allogeneic bone marrow transplantation (BMT) is the only potential cure for severe hemoglobinopathies. Typical regimens have used high doses of chemotherapy or chemo-radiotherapy to ablate recipient hematopoiesis and to prevent graft rejection. The widespread use of this treatment has been limited by toxicity, risk of end-organ damage, and donor availability. This study will use a nonmyeloablative regimen of fludarabine and busulfan to attempt to generate consistent engraftment with donor hematopoietic stem cells in patients with severe hemoglobinopathy.
G-CSF mobilization of the donor's peripheral blood white blood cells will precede donor apheresis. A nonmyeloablative conditioning regimen of fludarabine and busulfan will be administered to patients prior to allogeneic peripheral blood stem cell infusions. FK506 and prednisone will be administered for graft versus host disease (GVHD) prophylaxis. Patients will be evaluated for engraftment, donor: host hematopoietic chimerism, toxicity, and hemoglobinopathy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00034528
|United States, Massachusetts|
|Dana-Farber Cancer Institute/Harvard Cancer Center, Brigham and Women's Hospital and Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Catherine J. Wu, MD||Dana-Farber Cancer Institute|