Phase 1 ruxolitinib JAK1/2 inhibitor plus azacitidine DNA hypomethylating agent after alloHSCT

This Phase 1, single-site OHSU Knight Cancer Institute study tests safety, tolerability, and dose selection for post-transplant ruxolitinib (a JAK1/2 inhibitor; marketed as Jakafi by Incyte) given first as monotherapy, then combined with azacitidine (a DNA hypomethylating agent; marketed as Vidaza by Bristol Myers Squibb) as maintenance after reduced-intensity allogeneic hematopoietic stem cell transplantation for AML in complete remission. The goal is to reduce major post-alloHSCT failure modes: graft-versus-host disease (GVHD) and leukemia relapse; the trial’s two parts address (A) standard maintenance-eligible CR patients and (B) a cohort with graft failure. Scientifically, the bet is that JAK-STAT pathway suppression can prevent or blunt GVHD while azacitidine’s epigenetic reprogramming and anti-leukemic activity can help sustain remission without fully negating graft-versus-leukemia effects. Today’s care for alloHSCT-eligible AML in remission is reduced-intensity conditioning transplant with calcineurin inhibitor–based GVHD prophylaxis (often tacrolimus-based, sometimes with post-transplant cyclophosphamide) and close MRD/relapse monitoring; post-transplant maintenance is variable and center-dependent, with hypomethylating agents used in selected higher-risk situations but not universally standard.