NCT07411586

Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of Phase 1 is to find the recommended dose of ziftomenib and olutasidenib in patients with relapsed/refractory AML that has a mutation in the NPM1 and IDH1 genes. The goal of Phase 1b is to learn if the recommended dose of ziftomenib and olutasidenib found in Phase 1 can help to control the disease. The safety and effects of this combination will also be studied in both parts.

Detailed description

Primary Objectives: * Phase 1: To determine the safety and tolerability and recommended phase 2 dose (RP2D)) of ziftomenib and olutasidenib in adult patients with R/R NPM1 and IDH1 co-mutated AML * Phase 1b: To determine the preliminary efficacy of combination treatment as reflected by the composite remission rate (CRc=CR+ CRi +CRh) of ziftomenib and olutasidenib in adult patients with R/R NPM1 and IDH1 co-mutated AML Secondary Objectives: * To determine the overall response rate (ORR) including composite remission rate (CRc), partial remission (PR), and morphologic leukemia free state (MLFS) following therapy * To determine the duration of response (DOR), event-free survival (EFS), relapse-free survival (RFS), time to CRc, and overall survival (OS) following therapy * To determine the occurrence of minimal residual disease (MRD) negative response (CR/CRi) as assessed by multiparameter flow cytometry and NPM1m qPCR following therapy * To determine the time to achieve CR/CRi following initiation of therapy * To determine the rate of transfusion independence (TI) achieved by patients on therapy * To determine the proportion of patients that undergo allogeneic stem cell transplantation (alloSCT) following study therapy * To monitor longitudinal changes in IDH1m VAF in patients following treatment Exploratory Objective: • To perform detailed bulk and single cell multi-omics (DNA sequencing, RNA sequencing, global gene expression profiles, DNA methylation profiles), and other potential prognostic marker assays on longitudinally collected samples over the course of therapy to explore potential predictors of anti-tumor activity and/or resistance to treatment

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Ziftomenib	Given by mouth
DRUG	Olutasidenib	Given by mouth

Timeline

• Start date: 2026-08-31
• Primary completion: 2027-01-14
• Completion: 2029-01-14
• First posted: 2026-02-17
• Last updated: 2026-02-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study