SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation

This phase I trial tests the safety, side effects, and best dose of SNDX-5613 and gilteritinib for treating patients with acute myeloid leukemia that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) and has a mutation in the FLT3 gene along with either a mutation in the NMP1 gene or a type of mutation called a rearrangement in the MLL gene. SNDX-5613 is in a class of medications called menin inhibitors. It works by blocking the action of mutated MLL and NMP1 proteins that signal cancer cells to multiply. Gilteritinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of mutated FLT3 proteins that signal cancer cells to multiply. Giving SNDX-5613 with gilteritinib may be safe, tolerable and/or effective in treating patients with relapsed/refractory FLT3 mutated acute myeloid leukemia.

PRIMARY OBJECTIVE: I. To determine the safety of revumenib (SNDX-5613) + gilteritinib. SECONDARY OBJECTIVES: I. To determine the preliminary efficacy of SNDX- 5613+ Gilteritinib. EXPLORATORY OBJECTIVES: I. To perform pharmacokinetic and pharmacodynamics assessments of the study drug combination. OUTLINE: This is a dose-escalation study. Patients receive SNDX-5613 orally (PO) twice per day (BID) and gilteritinib PO once per day (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiogram (ECHO) or multigated acquisition (MUGA) scan during screening, as well as bone marrow biopsy and aspiration and blood sample collection throughout the study. After completion of study treatment patients are followed up at 30 days and then every 6 months for up to 2 years.