Objective:
Primary Objective:
The primary objective of the randomized, dose finding portion of the trial is to compare the safety, feasibility, and efficacy of two ruxolitinib doses in the setting of GVHD prophylaxis. In this portion of the study, these three evaluations will be assessed by:
- Safety: graft failure by Day 28 and overall mortality by Day 100
- Feasibility: proportion of participants requiring dose reduction or interruption by Day 100
- Efficacy: Grade II-IV acute GVHD-free survival by Day 100
The primary objective of the randomized Phase III portion of the trial is to compare GFS up to 24 months after HCT between Tac/MTX/Rux versus PTCy/Tac/MMF. There are co-primary objectives of demonstrating non-inferiority and superiority on the primary endpoint of GFS. An event for this time to event outcome is defined as Grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, or death by any cause.
Secondary Objectives:
Secondary objectives are the following comparisons between the two treatments in the Phase III portion based on:
- GVHD-free and relapse/progression-free survival
- Rates of NIH mild, moderate, and severe chronic GVHD (defined by the NIH Consensus Conference Criteria)
- Grade II-IV and III-IV acute GVHD per the NIH Consensus Conference Criteria on Acute GVHD Grading by Day +180
- Hematologic recovery including neutrophil engraftment, platelet engraftment, lymphocyte recovery
- Proportion of participants with full (at least 95% or more) or mixed (5.0-94.9%) total donor chimerism or graft rejection (less than 5% total donor chimerism)
- Graft failure
- Disease relapse or progression
- Non-relapse mortality (NRM)
- Toxicity and Infections
- Disease-free survival
- OS
- PRO