PRIMARY OBJECTIVE:~I. To compare the 100-day acute grade 2-4 GvHD rate to matched controls.~SECONDARY OBJECTIVES:~I. To compare the 1-year rate of GvHD-free, relapse-free survival to matched controls.~II. To assess the time to neutrophil and platelet engraftment. III. To assess the toxicity profile associated with this regimen. IV. To assess the incidence of severe grade 3-4 acute GVHD. V. To assess the incidence of limited, extensive, and moderate to severe chronic GVHD.~VI. To assess the incidence of disease relapse. VII. To assess the incidence of non-relapse mortality. VIII. To assess overall survival and progression-free survival. IX. To assess immunosuppression discontinuation rate.~TERTIARY OBJECTIVE (CORRELATIVE STUDY):~I. Immune recovery and cytokines at various time points pre- and post- transplant~OUTLINE:~CONDITIONING: Patients receive busulfan intravenously (IV) over 3 hours on days -20, -13, and -6 to -3, thiotepa IV on day -7, and fludarabine IV over 1 hour on days -6 to -3.~STEM CELL TRANSPLANT: Patients undergo stem cell transplant on day 0.~GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4. Patients also receive itacitinib orally (PO) once daily (QD) on days 5-60 in the absence of disease progression or unacceptable toxicity. Beginning day 5 after stem cell transplant, patients also receive tacrolimus IV over 24 hours until able to tolerate oral tacrolimus, whereby patients then receive tacrolimus PO twice daily (BID).~After completion of study intervention, patients are followed up at days 100, 180, and 365 after stem cell transplant.
This phase II trial studies if itacitinib plus standard of care treatment may help prevent graft-versus-host-disease (GVHD) in patients who have received an allogeneic (donor) stem cell transplant. An allogeneic transplant uses blood-making cells from a family member or unrelated donor to remove and replace a patient's abnormal blood cells. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Giving itacitinib with standard of care treatment after the transplant may stop this from happening.