This trial studies how well fludarabine-based reduced intensity conditioning regimen works in preventing transplant rejection in patients with aplastic anemia or inherited bone marrow failure syndromes scheduled to undergo donor bone marrow transplant. Reduced intensity conditioning involves giving medicines that decrease the amount of white blood cells in the body. These cells support the immune system which fights infection and also help the body identify anything that is new and determine if it needs to get rid of it. Decreasing the amount of white blood cells may help the new bone marrow to get accepted and not be rejected by the body’s immune system.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02928991.
PRIMARY OBJECTIVES:
I. Determination of time to engraftment, as well as rates of primary and secondary graft failure, and acute and chronic graft versus host disease (GvHD) following matched related donor bone marrow transplant (MRD- BMT) for patients with acquired aplastic anemia (AA) or inherited bone marrow failure (iBMF) syndromes receiving fludarabine-based conditioning regiments.
II. Defining the correlation between the degree of donor chimerism achieved following MRD-BMT in patients with acquired AA or iBMF syndromes and overall survival, graft failure, elimination of clonal hematopoiesis, and quality of immune reconstitution.
SECONDARY OBJECTIVES:
I. To determine the rate of event-free survival with stable donor engraftment at one year for patients with acquired AA receiving MRD-BMT following reduced intensity conditioning (RIC) including anti-thymocyte globulin (ATG), fludarabine, and dose-reduced cyclophosphamide.
II. To determine the rate of overall survival with stable donor engraftment at one year for patients with defined iBMF syndromes receiving MRD-BMT with fludarabine-based, disease specific conditioning.
OUTLINE: Patients are assigned to 1 of 3 arms.
ARM I (ACQUIRED APLASTIC ANEMIA): Patients receive fludarabine on days -7 to -3, cyclophosphamide on days -5 and -4, rabbit anti-thymocyte globulin on days -4 to -2, and cyclosporine intravenously (IV) beginning day -1 (cyclosporine is switched to tacrolimus orally [PO] when patient can tolerate, slow wean beginning 180 days post-transplant). Patients undergo bone marrow transplantation on day 0.
ARM II (iBMF SYNDROMES WITH TRILINEAGE APLASIA): Patients receive fludarabine on days -7 to -3, cyclophosphamide on days -6 to -3, rabbit anti-thymocyte globulin on days -4 to -2, and cyclosporine IV beginning day -1 (cyclosporine is switched to tacrolimus PO when patient can tolerate, slow wean beginning 100 days post-transplant). Patients undergo bone marrow transplantation on day 0, then receive mycophenolate mofetil (MMF) PO thrice daily (TID) on days 1-45.
ARM III (iBMF SYNDROMES WITHOUT TRILINEAGE APLASIA): Patients receive rabbit anti-thymocyte globulin on days -10 to -8, busulfan IV every 6 hours (Q6H) or once daily (QD) on days -7 to -4, fludarabine on days -6 to -2, and cyclosporine IV beginning day -1 (cyclosporine is switched to tacrolimus PO when patient can tolerate, slow wean beginning 100 days post-transplant). Patients undergo bone marrow transplantation on day 0, then receive MMF PO TID on days 1-45.
After completion of the bone marrow transplant, patients are followed up for 3 years.
Lead OrganizationChildren's Hospital of Philadelphia
Principal InvestigatorTimothy Steven Olson
