NCT04065399

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

A Phase 1/2, Open-label, Dose-Escalation and Dose-Expansion Cohort Study of SNDX-5613 in Patients With Relapsed/Refractory Leukemias, Including Those Harboring an MLL/KMT2A Gene Rearrangement or Nucleophosmin 1 (NPM1) Mutation

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 447 (estimated)
• Sponsor: Syndax Pharmaceuticals · Industry
• Sex: All
• Age: 30 Days
• Healthy volunteers: Not accepted

Summary

Phase 1 dose escalation will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of revumenib in participants with acute leukemia. In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib.

Detailed description

Phase 1: Oral revumenib; sequential cohorts of escalating dose levels of revumenib to identify the MTD and RP2D. Participants will be enrolled in one of six dose-escalation arms: Arm A: Participants not receiving any strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducers or fluconazole. Arm B: Participants receiving itraconazole, ketoconazole, posaconazole, or voriconazole (strong CYP3A4 inhibitors) for antifungal prophylaxis. Arm C: Participants receiving revumenib and cobicistat. Arm D: Participants receiving fluconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis. Arm E: Participants not receiving any weak, moderate, or strong CYP3A4 inhibitors/inducers. Arm F: Participants receiving isavuconazole (moderate CYP3A4 inhibitor) for antifungal prophylaxis. In Phase 2, participants will be enrolled in 4 indication-specific expansion cohorts to determine the efficacy, short- and long-term safety, and tolerability of revumenib: * Cohort 2A: Participants with KMT2Ar acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia (MPAL) * Cohort 2B: Participants with KMT2A AML * Cohort 2C: Participants with NPM1m AML * Cohort 2D: Participants with acute leukemia (including KMT2Ar, NPM1m, NUP98r and other acute leukemias expected to have HOX/MEIS upregulation)

Conditions

• Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia
• Mixed Lineage Acute Leukemia
• Mixed Phenotype Acute Leukemia
• Acute Leukemia of Ambiguous Lineage

Interventions

Type	Name	Description
DRUG	revumenib	revumenib orally
DRUG	cobicistat	Phase 1 Arm C participants will receive 150 mg cobicistat daily.

Timeline

• Start date: 2019-11-05
• Primary completion: 2027-12-15
• Completion: 2027-12-15
• First posted: 2019-08-22
• Last updated: 2026-03-18

Locations

57 sites across 11 countries: United States, Australia, Canada, France, Germany, Israel, Italy, Lithuania, Netherlands, Puerto Rico, Spain

Regulatory

• FDA-regulated drug study