The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of revumenib in combination with intensive chemotherapy in participants with newly diagnosed acute myeloid leukemia (AML) harboring alterations in KMT2A, NPM1, or NUP98 genes.
The Dose Escalation portion of this study will identify the maximum tolerated dose, or if different, the recommended Phase 2 dose of revumenib to be used in combination with intensive chemotherapy and in maintenance monotherapy following intensive chemotherapy in participants with newly diagnosed AML harboring alterations in KMT2A, NPM1, or NUP98 genes. In the Dose Expansion portion of the study, safety and preliminary efficacy of revumenib may be explored in expansion cohorts at tolerated dose levels. In both Dose Escalation and Dose Expansion, the treatment period will consist of an induction phase (up to 2 cycles), a consolidation phase (up to 4 cycles and could include hematopoietic stem cell transplant for participants who are transplant eligible and have an available donor), and a maintenance monotherapy phase with revumenib. The cycle duration will be 28 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
96
Participants will receive revumenib orally during Induction, Consolidation, and Maintenance until meeting criteria for discontinuation.
Induction: Participants will receive an intravenous (IV), 2-drug combination of cytarabine and either daunorubicin or idarubicin.
Consolidation: Participants will receive HiDAC IV.
Dose Escalation: Number of Participants with Dose-limiting Toxicities
Time frame: Up to Day 42
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 through 30 days after final dose (up to approximately 3 years)
Maximum Plasma Concentration (Cmax) of Revumenib and its Major Metabolite
Time frame: Predose through Day 15
Area Under the Plasma Concentration Versus Time Curve From Time 0 to t (AUC0-t) of Revumenib and its Major Metabolite
Time frame: Predose through Day 15
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