NCT07153497Not yet recruitingPhase 2

Testing the Use of an IDH1 Inhibitor, Olutasidenib, in Acute Myeloid Leukemia Added to ASTX727 and Venetoclax; in High-Risk MDS Added to ASTX727; and Alone in Low Risk MDS (A MyeloMATCH Treatment Substudy)

A Randomized Phase 2 Trial of Olutasidenib-Based Therapies in Patients With Newly Diagnosed IDH1-Mutant Myeloid Malignancies: A MyeloMATCH Substudy

Source: ClinicalTrials.gov · Last updated 9 Sept 2026

Brief summary (registry, in English)

This phase II MyeloMATCH treatment substudy tests the addition of olutasidenib to usual treatment in patients with higher-risk myelodysplastic syndrome (MDS) or patients with acute myeloid leukemia (AML) with a mutation in the IDH1 gene. Olutasidenib blocks the protein made by the mutated IDH1 gene. Blocking this protein may help keep cancer cells from growing. For patients with MDS, olutasidenib will be added to decitabine-cedazuridine (also called ASTX727). Decitabine is in a class of medications called hypomethylating agents and is the standard treatment for MDS. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. The cedazuridine makes it possible to take the decitabine by mouth. Adding olutasidenib to the usual treatment for MDS (ASTX727) may increase the likelihood of going into remission. For patients with AML, olutasidenib and ASTX727 will be combined with venetoclax, a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Adding olutasidenib to the usual treatment for AML (ASTX727 and venetoclax) may increase the likelihood of going into remission. For low risk MDS, the substudy tests whether giving olutasidenib alone helps improve blood counts.

Status (registry): Not yet recruiting
Phase (registry): Phase 2
Study type: Interventional
Enrollment: 132 (estimated)
First submitted: 3 Sept 2025
Start date: 27 Nov 2026
Primary completion date: 26 Apr 2030
Lead sponsor: National Cancer Institute (NCI)
Diseases: Myelodysplastic syndromes, Acute myeloid leukemia
NCT number: NCT07153497

What you commit to

Study type: Interventional · Phase 2
Planned participants: 132
From 27 Nov 2026 to the primary completion date, 26 Apr 2030
No sites listed in no country
Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Who the study is looking for

Patient must be enrolled on the MYELOMATCH Master Screening and Reassessment Protocol (MSRP), determined to have an IDH1-R132 mutation and assigned to this trial via MATCHBox
REGISTRATION ELIGIBILITY CRITERIA (STEP 1):
Documentation of IDH1 mutated MDS or AML
COHORT A: Age ≥ 60 years or adults ˂ 60 and ≥ 18 who in the opinion of the treating physician are not candidates for intensive, cytarabine-based induction based on clinical status (i.e., performance status), organ dysfunction, or disease biology with a morphologically confirmed diagnosis of AML with ≥ 20% myeloblasts in the bone marrow or peripheral blood
COHORT B: Age ≥ 18 years with treatment-naïve HR-MDS with an IPSS-R score ≥ 4.0 at time of enrollment
COHORT C: Age ≥ 18 years with LR-MDS with an IPSS-R score ≤ 3.5 at time of enrollment and either:
- RBC-TD anemia (≥ 2 units/8 weeks in the 16 weeks prior to registration) who have failed or are ineligible to erythropoiesis-stimulating agents (ESA) therapy
- Presence of either neutropenia (\< 1 x 10\^9/L) or thrombocytopenia (\< 100 x 10\^9/L) for use as frontline therapy or after failure of prior therapies, including growth factors. Patient must be hypomethylating agent (HMA)-naïve
No prior therapy excluding:
- Cohort A: hydroxyurea and all-trans retinoic acid (ATRA) for AML
- Cohort B: ESAs (erythropoiesis-stimulating agents) and/or TGF-β inhibitors for HR-MDS
- Cohort C: ESAs (erythropoiesis-stimulating agents, TGF-β inhibitors, telomerase inhibitors, and/or G-CSF for LR-MDS)
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 3
Creatinine clearance ≥ 30 mL/min (using the Cockcroft-Gault equation)
Total bilirubin ≤ 3 x upper limit of normal (ULN)
- Unless the increase is due to Gilbert's disease as determined per physician discretion/institutional practice
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x upper limit of normal (ULN)
Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effect on the developing fetus and newborn are unknown
- Therefore, for women of childbearing potential only, a negative pregnancy test must be done ≤ 7 days prior to registration. (Cohorts B and C only)
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. A corrected QT interval \< 480 msec (calculated using the Fridericia's formula \[QTcF\]) excluding patients with a right bundle branch block (RBBB) after approval of the principal investigator (PI)
No known medical condition causing an inability to swallow, tolerate oral medications and must have no known malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or small bowel resection) that may significantly alter the absorption of the study drugs
RE-REGISTRATION ELIGIBILITY CRITERIA FOR COHORT B, ARM 3 (STEP 2): Patients on the ASTX727 monotherapy arm (Cohort B-Arm 3) that do not achieve a CR (complete response), CRL (CR with limited count recovery), or CRh (CR with partial count recovery) after completing 6 cycles of study treatment
RE-REGISTRATION ELIGIBILITY CRITERIA FOR COHORT B, ARM 3 (STEP 2): ECOG Performance Status ≤ 3
RE-REGISTRATION ELIGIBILITY CRITERIA FOR COHORT B, ARM 3 (STEP 2): Creatinine clearance ≥ 30 mL/min (using the Cockcroft-Gault equation)
RE-REGISTRATION ELIGIBILITY CRITERIA FOR COHORT B, ARM 3 (STEP 2): Total bilirubin ≤ 3 x upper limit of normal (ULN)
- Unless the increase is due to Gilbert's disease as determined per physician discretion/institutional practice
RE-REGISTRATION ELIGIBILITY CRITERIA FOR COHORT B, ARM 3 (STEP 2): AST (SGOT)/ALT (SGPT) ≤ 3 x upper limit of normal (ULN)

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

This page is information, not medical advice. Discuss any trial with your doctor.