Azacitidine, Venetoclax and NK Cells in Newly Daignosed Older/Unfit AML

Summary: 

Older patients with adverse-risk acute myeloid leukemia (AML) have dismal outcomes with a 3-year survival of roughly 20%. Twenty to 50% of newly diagnosed older patients with AML do not respond to current standard frontline therapy, with high rates of refractory disease in adverse-risk patients. Stem cell transplantation (SCT) can be potentially curative, however, only 10% of older/unfit patients can undergo SCT. SCT is also associated with a significant risk of death of 5% to 20% and side effects are noted in 80% of patients, including recurrent infections and acute and chronic graft-vs-host disease. Hence, novel therapies are urgently needed to improve outcomes in older/unfit patients with newly diagnosed AML.​ The researchers hypothesize that combining epigenetic therapy, apoptosis targeting, and cellular immunotherapy using azacitidine, venetoclax, and allogeneic NK cells, respectively, will improve outcomes in patients with AML compared to either azacitdine/Venetoclax alone or NK cells alone.​ This phase I study will assess the safety of this three drug combination in newly diagnosed older/unfit patients with AML and myelodysplastic syndrome (MDS). This will be the first trial to use azacitdine with venetoclax prior to cellular therapy approach in any cancer, as opposed to cytotoxic chemotherapy based lymphodepletion regimens. Furthermore, this clinical trial can potentially transform the standard treatment approach as well as landscape of emerging therapies for older, unfit, or transplant-ineligible patients.​

Trial Registration: ClinicalTrials.gov Identifier: NCT05834244