Phase 1 arsenic trioxide p53-reactivating agent with fludarabine/busulfan allo-HSCT in AML/MDS

University of Michigan Rogel Cancer Center is running this Phase 1, non-randomized study testing whether adding arsenic trioxide (ATO)—a small molecule reported to help restore wild-type conformation/function of some mutant p53 proteins—around allogeneic hematopoietic stem cell transplantation can reduce relapse in high-risk, TP53-mutated AML or MDS. Patients receive ATO IV on days -6 to -2 and +1 to +5, alongside standard reduced-intensity conditioning with fludarabine (purine analog inhibiting DNA synthesis) and busulfan (alkylating agent causing DNA crosslinking), followed by donor stem cell infusion on day 0, with serial marrow and blood sampling. The main goals are safety/tolerability and dose finding in the peri-transplant window, where overlapping hepatic and marrow toxicities are practical concerns. Commercially, ATO is a generic drug (historically developed and marketed as Trisenox by Teva) being repositioned as a biomarker-defined, transplant-adjunct strategy rather than a frontline cytotoxic. Today’s care for TP53-mutated AML/MDS often uses azacitidine or decitabine plus venetoclax for induction/bridging when feasible, then allo-transplant in responders—yet relapse risk remains high, making a low-cost “maintenance-like” peri-transplant approach an attractive angle.