Azacitidine, Venetoclax, and Gilteritinib in Treating Patients With Recurrent/Refractory FLT3-Mutated Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or High-Risk Myelodysplastic Syndrome/Myeloproliferative Neoplasm
Key claim: A phase I/II trial is evaluating whether adding the FLT3 inhibitor gilteritinib to azacitidine plus venetoclax improves outcomes in patients with recurrent/refractory FLT3-mutated AML, CMML, or high-risk MDS/MPN compared to the doublet alone.
Abstract
This phase I/II trial studies the side effects and best dose of gilteritinib and to see how well it works in combination with azacitidine and venetoclax in treating patients with FLT3-mutation positive acute myeloid leukemia, chronic myelomonocytic leukemia, or high-risk myelodysplastic syndrome/myeloproliferative neoplasm that has come back (recurrent) or has not responded to treatment (refractory). Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gilteritinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine, venetoclax, and gilteritinib may work better compared to azacitidine and venetoclax alone in treating patients with acute myeloid leukemia, chronic myelomonocytic leukemia, or myelodysplastic syndrome/myeloproliferative neoplasm.
Why this matters
FLT3 mutations are uncommon in CMML and MDS/MPN overlap but, when present, define a high-risk molecular subgroup that has historically been managed by extrapolation from AML. Adding gilteritinib to an azacitidine + venetoclax backbone tests whether AML-style molecularly targeted triplet therapy translates to these overlap entities, where prospective data in FLT3-mutated subsets are essentially absent.