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

NCT06465953 · tracked via the Priya Life Science Netherlands tracker

Sponsor

Institut de Recherches Internationales Servier

Phase

Phase 3

Started

2024-12-03

Last updated

2026-09-03

Condition(s) studied

Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS)Myelodysplastic Syndromes (MDS)

Investigational drug(s) / intervention(s)

Ivosidenib →Azacitidine →

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.

Study 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

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

Primary outcome measure(s)

Number of participants achieving CR and PR by 4 months — Through 4 months after starting treatment
Complete remission (CR) or Partial remission (PR) as per International Working Group (IWG) 2006 criteria

Trial sites (62)

Facility	City	Region	Status
Presbyterian / St. Luke'S Medical Center	Denver	Colorado	Recruiting
University of Chicago, Duchossois Center for Advanced Medicine (DCAM)	Chicago	Illinois	Recruiting
Massachusetts General Hospital	Boston	Massachusetts	Recruiting
MSKCC	New York	New York	Recruiting
Unc Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	Recruiting
Ohio State University Comprehensive Cancer Center	Columbus	Ohio	Recruiting
Oncology Associates of Oregon	Eugene	Oregon	Recruiting
University of Texas UT Southwestern Comprehensive Cancer Center	Dallas	Texas	Recruiting
MD Anderson Cancer Centre	Houston	Texas	Recruiting
Royal Adelaide Hospital	Adelaide	Australia	Not Yet Recruiting
Monash Health	Clayton	Australia	Recruiting
Northern Health	Epping	Australia	Recruiting
Liverpool Hospital	Liverpool	Australia	Not Yet Recruiting
Sir Charles Gairdner Hospital	Nedlands	Australia	Recruiting
Calvary Mater Newcastle	Waratah	Australia	Recruiting
Liga Paranaense de Combate ao Câncer - Hospital Erasto Gaertner	Curitiba	Brazil	Recruiting
Centro de Pesquisa Clínica - Hospital Nove de Julho	São Paulo	Brazil	Recruiting
Real E Benemérita Associação Portuguesa de São Paulo	São Paulo	Brazil	Recruiting
Hospital das Clínicas da Faculdade de Medicina da USP	São Paulo	Brazil	Recruiting
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein	São Paulo	Brazil	Recruiting
Casa de Saúde Santa Marcelina	São Paulo	Brazil	Recruiting
Centro de Pesquisas Clínicas da Fundação Doutor Amaral Carvalho	São Paulo	Brazil	Recruiting
Instituto Nacional do Câncer	São Paulo	Brazil	Not Yet Recruiting
Chu Nantes-Hotel Dieu	Nantes	France	Recruiting
Chu de Nice - Hôpital L'Archet 1	Nice	France	Recruiting
Hopital Saint Louis	Paris	France	Recruiting
Chu Bordeaux, Hopital Du Haut Leveque	Pessac	France	Recruiting
Institut Universitaire Du Cancer Toulouse-Oncopole	Toulouse	France	Recruiting
Chu Brabois	Vandœuvre-lès-Nancy	France	Recruiting
Universitatsklinikum Dresden Carl Gustav Carus	Dresden	Germany	Recruiting
Marien Hospital Duesseldorf	Düsseldorf	Germany	Recruiting
Universitaetsmedizin Goettingen (Umg)	Göttingen	Germany	Recruiting
Universitaetsklinikum Leipzig	Leipzig	Germany	Recruiting
Tum Klinikum Rechts Der Isar	Munich	Germany	Recruiting
Azienda Ospedaliero Universitaria Delle Marche	Ancona	Italy	Recruiting
Istituto Di Ematologia "Lorenzo E Ariosto Seragnoli" - Policlinico Di S. Orsola	Bologna	Italy	Recruiting
Azienda Ospedaliero-Universitaria Careggi	Florence	Italy	Recruiting
Humanitas Research Hospital (Istituto Clinico Humanitas)	Milan	Italy	Recruiting
Fondazione I.R.C.C.S. Policlinico San Matteo	Pavia	Italy	Recruiting
Dipartimento Di Biomedicina E Prevenzione - Universita Degli Studi Di Roma "Tor Vergata"	Roma	Italy	Recruiting

+ 22 more sites — see the full list on the official registry below.

More Institut de Recherches Internationales Servier trials in the Netherlands

Phase III Study in First-line Treatment of Patients With Metastatic Colorectal Cancer Who Are Not Candidate for Intensive Therapy. Active, not recruiting

Safety Study of AG-120 or AG-221 in Combination With Induction and Consolidation Therapy in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) With an IDH1 and/or IDH2 Mutation Active, not recruiting

Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO) Active, not recruiting

Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Participants With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation Active, not recruiting

Vorasidenib in Combination With Temozolomide (TMZ) in IDH-mutant Glioma Active, not recruiting

Other trials for the same condition

A Study to Evaluate Long-term Safety in Participants Who Have Participated in Other Luspatercept (ACE-536) Clinical Trials Recruiting

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06465953 on ClinicalTrials.gov ↗ ← All trials in the Netherlands