Recruiting

Phase 3

Ivosidenib vs. AzacitidineIvosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation

Sponsor:

Institut de Recherches Internationales Servier

Code:

NCT06465953

Conditions

Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS)

Myelodysplastic Syndromes (MDS)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Ivosidenib

Azacitidine

Study Details

Brief summary:

This study will enroll participants with myelodysplastic syndromes (MDS) with an Isocitrate dehydrogenase protein, 1 (IDH1) mutation, who have not received treatment with a hypomethylating agent previously. Participants will be randomized to receive either ivosidenib (IVO) alone or azacitidine (AZA) alone. IVO will be administered daily throughout the 28-day treatment cycle and AZA will be administered for the first 7 days of each 28-day cycle. Study visits will be conducted every week during Cycle 1 (Days 1, 8, 15, and 22), and Day 1 of each cycle thereafter. After the last dose of treatment, participants will attend an safety follow-up visit and participants will be followed to assess overall survival. Study visits may include a bone marrow aspirate, physical exam, echocardiogram (ECHO), electrocardiogram (ECG), blood and urine analysis, and questionnaires.

Conditions

Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS)

Myelodysplastic Syndromes (MDS)

Study ID

NCT06465953

Start date

Dec 3, 2024

Status verified date

Sep, 2026

Completion date

Dec 1, 2028

Anticipated

Primary completion date

Nov 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Diagnosis of HMA naive IDH1 R132 mutated MDS defined according to WHO criteria (5th edition):
Moderate high, high and very high-risk MDS per IPSS-M score will be eligible regardless of blood counts and with blast counts 0-19%.
Low and moderate low-risk MDS per IPSS-M score must:
Have cytopenias related to MDS, defined as: <100 platelets/microliter, or absolute neutrophil count (ANC) <1000/mm3, or hemoglobin <10g/dL AND
Have a blast count between 5-19% AND
Be eligible for HMA therapy (very low risk participants are to be excluded)
Locally or centrally confirmed IDH1 R132 C/G/H/L/S mutation

Exclusion Criteria:

Received prior anticancer/disease modifying treatment for MDS (including HMA's, cytotoxic chemotherapy, investigational agents, bcl-2 inhibitor based-regimens, hematopoietic stem cell transplant (HSCT), IDH1 inhibitors). For LR-MDS patients, prior treatment with growth factors, luspatercept, lenalidomide, and imetelstat are allowed.
>20% blasts by morphology or immunohistochemistry on screening bone marrow aspirate/biopsy

Study Design

Enrollment

48 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Ivosidenib monotherapy

experimental: Azacitidine monotherapy

Interventions

Ivosidenib

Two 250 mg tablets, totaling 500 mg, administered orally once daily until disease relapse or progression, unacceptable toxicity, confirmed pregnancy, undergoing HSCT, death, withdrawal of consent, lost to follow-up, or Sponsor ending the study, whichever occurs first.

Azacitidine

Azacitidine 75mg/m\^2/day administered by subcutaneous (SC) or intravenous (IV) injection for 1 week (7 days) of each 4-week (28 day) treatment cycle until disease relapse or progression, unacceptable toxicity, confirmed pregnancy, undergoing HSCT, death, withdrawal of consent, lost to follow-up, or Sponsor ending the study, whichever occurs first.

Primary outcome measure

Number of participants achieving CR and PR by 4 months [ Time Frame: Through 4 months after starting treatment ]

Central Contacts and Locations

Central contacts

Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department

+33 1 55 72 60 00 scientificinformation@servier.com

Locations

Presbyterian / St. Luke'S Medical Center

Recruiting

Denver, Colorado, United States, 80218

University of Chicago, Duchossois Center for Advanced Medicine (DCAM)

Recruiting

Chicago, Illinois, United States, 60637

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Andrew Brunner

617-724-1124 abrunner@mgb.org

MSKCC

Recruiting

New York, New York, United States, 10065

Unc Lineberger Comprehensive Cancer Center

Recruiting

Chapel Hill, North Carolina, United States, 27514

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Oncology Associates of Oregon

Recruiting

Eugene, Oregon, United States, 97401

University of Texas UT Southwestern Comprehensive Cancer Center

Recruiting

Dallas, Texas, United States, 75235

MD Anderson Cancer Centre

Recruiting

Houston, Texas, United States, 77030

More Information

Sponsor

Institut de Recherches Internationales Servier

Last update posted

Sep 3, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Institut de Recherches Internationales Servier on 2026-09-03.