Oral Azacitidine (CC-486) Epigenetic Priming and Maintenance for Adult Acute Myeloid Leukemia (AML) Patients

A significant proportion of patients with Acute myeloid leukemia (AML) who are fit to receive intensive chemotherapy and reach first complete remission (CR), relapse despite further high or low intensity therapies. Relapse/refractory (R/R) AML generally portends poor outcomes and available agents to treat this condition have modest efficacy. Until the recent approval of CC-486 as a maintenance therapy, no other drug had shown overall survival (OS) advantage for patients with AML in first complete remission (CR1). In the CC-486 registration trial (QUAZAR AML-01), remission induction was achieved by intensive chemotherapy, but patients were ineligible to proceed to allogeneic stem cell transplant (ASCT) at the time of screening. Post CR1, CC-486 apart from prolonging remission was also successful in deepening the quality of remission by eradicating measurable residual disease (MRD). It is therefore logical to investigate the feasibility of CC-486 as a consolidation regimen from the time of CR1, in patients eligible for curative intent ASCT. It is anticipated that continued epigenetic priming peri-ASCT with CC-486 can favorably alter disease biology for AML patients in CR1, modulate immune surveillance to decrease relapse risk, mitigate adverse graft versus host disease (GVHD) biology without significant compromise on the quality of life. This pilot study will assess the suitability of CC-486 as a bridge to transplant, will help optimize the timing between CC-486 administration and the start of transplant preparative regimen, and will assess the utility of continued CC-486 maintenance post-transplant.