NCT06543381

Olutasidenib for the Treatment of Patients With IDH1 Mutated AML, MDS or CMML After Donor Hematopoietic Cell Transplant

Pilot Trial of Olutasidenib Maintenance Post Allogeneic Hematopoietic Cell Transplantation in Patients Carrying IDH1 Mutation With AML, MDS, or CMML Disease

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and effectiveness of olutasidenib in preventing the return of disease (relapse) in patients who have undergone donor (allogeneic) hematopoietic cell transplant for acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML) carrying an IDH1 mutation. Olutasidenib is in a class of medications called IDH1 inhibitors. It works by slowing or stopping the growth of cancer cells. Giving olutasidenib may be safe, tolerable and/or effective in preventing relapse in patients with IDH1 mutated AML, MDS or CMML after an allogeneic hematopoietic cell transplant.

Detailed description

PRIMARY OBJECTIVE: I. Evaluate the safety and tolerability of olutasidenib as maintenance therapy after allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). SECONDARY OBJECTIVES: I. Assess overall survival (OS) and leukemia-free survival (LFS) at 1 and 2 years after first dose of olutasidenib. II. Estimate cumulative incidence of relapse (CIR), non-relapse mortality (NRM), graft-versus-host disease (GVHD) free, relapse-free survival (GRFS) at 1 and 2 years after first dose of olutasidenib. III. Rate and grading of acute GVHD of grades 2-4 and 3-4 at day 100 post allogeneic HCT. IV. Incidence and grading of chronic GVHD of all grades at 1 and 2 years after first dose of olutasidenib. EXPLORATORY OBJECTIVES: I. Monitor disease status by multiparameter flow cytometry among a subset of patients with minimal residual disease (MRD)+ disease when starting olutasidenib. II. Molecular monitoring of disease status by HopeSeq complete (at City of Hope \[COH\]) and equivalent next generation sequencing (NGS) assay at Cleveland Clinic. III. Monitor immune reconstitution by flow cytometry during protocol therapy. IV. Mutant (m)IDH1 testing on peripheral blood samples with standard polymerase chain reaction (PCR). V. Investigate IFN-ɣ signaling in immune cell subsets before and during maintenance therapy. VI. Monitor mIDH1 variant allele fraction (VAF) by droplet digital PCR (ddPCR) beads, emulsion, amplification, magnetics (BEAM)ing technology on peripheral blood. OUTLINE: Starting 50-120 days after bone marrow transplant, patients receive olutasidenib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study. After completion of study treatment, patients are followed up at 30 days and then up to 2 years.

Conditions

• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Myelodysplastic Syndrome

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Olutasidenib	Given PO

Timeline

• Start date: 2025-01-17
• Primary completion: 2027-02-05
• Completion: 2027-02-05
• First posted: 2024-08-09
• Last updated: 2026-03-05

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study