This phase II trial studies the side effects and how well giving antithymocyte globulin, fludarabine phosphate, and cyclophosphamide together with total body-irradiation (TBI) followed by a donor bone marrow transplant (BMT) works in treating patients with sickle cell anemia. Giving chemotherapy, such as fludarabine phosphate and cyclophosphamide, and TBI before a donor bone marrow transplant helps stop the growth of abnormal cells. It also stops 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 antithymocyte globulin before transplant and sirolimus and mycophenolate mofetil (MMF) after transplant may stop this from happening.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT00489281.
OBJECTIVES:
I. Obtain estimates of transplant-related mortality (TRM) and progression-free survival in patients with sickle cell disease receiving non-myeloablative conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow from first-degree relatives (“mini-haploBMT”).
II. Characterize donor hematopoietic chimerism in peripheral blood at days ~30, ~60, and ~180 after mini-haplo BMT.
III. Characterize hematologic and non-hematologic toxicities of mini-haplo BMT.
OUTLINE:
PREPARATIVE REGIMEN: Patients receive antithymocyte globulin intravenously (IV) over 6 hours on day -9 and over 4 hours on days -8 and -7. Patients also 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 TBI on day -1.
TRANSPLANTATION: Patients undergo donor BMT on day 0. Patients then receive cyclophosphamide IV over 1-2 hours on days 3 and 4.
GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive sirolimus orally (PO) once daily (QD) on days 5-365 and MMF PO thrice daily (TID) on days 5-35.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at days 30, 60, 180, and 365 and then annually thereafter.
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorJavier Bolanos Meade
