A Randomized, Multi-Center, Phase III Trial of Calcineurin Inhibitor-Free Interventions for Prevention of Graft-versus-Host Disease

The study is designed as a three arm randomized Phase III, multicenter trial comparing two calcineurin inhibitor (CNI)-free strategies for GVHD prophylaxis to standard calcineurin inhibitor tacrolimus and methotrexate (Tac/Mtx) in patients with acute leukemia or myelodysplasia undergoing myeloablative conditioning hematopoietic stem cell transplantation. Primary Objective: The primary objective of the randomized trial is to compare chronic GVHD/relapse-free survival [CRFS] as a time to event endpoint after hematopoietic stem cell transplant (HSCT) between each of the CNI-free interventions and a Tac/Mtx control. Secondary Objectives: Secondary objectives are: comparison of rates of grade II-IV and III-IV acute GVHD, chronic GVHD, chronic GVHD-free survival, immunosuppression-free survival at one year, neutrophil and platelet engraftment, disease relapse, transplant-related mortality, rates of Grade . 3 toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0; incidence of CMV and EBV reactivation, incidence of infections; immune reconstitution, quality of life and overall survival.