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

September 2, 2026 updated by: Institut de Recherches Internationales Servier

A Phase 3, Multicenter, Open Label, Randomized, Non-comparative Two-arm Study of Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Adult Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an Isocitrate Dehydrogenase-1 (IDH1) Mutation (PyramIDH Study)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
  • Phone Number: +33 1 55 72 60 00
  • Email: scientificinformation@servier.com

Study Locations

  • Australia
      • Adelaide, Australia, 5000
        • Not yet recruiting
        • Royal Adelaide Hospital
      • Clayton, Australia, 3168
        • Recruiting
        • Monash Health
      • Epping, Australia, 3076
        • Recruiting
        • Northern Health
      • Liverpool, Australia, 2170
        • Not yet recruiting
        • Liverpool Hospital
      • Nedlands, Australia, 6009
        • Recruiting
        • Sir Charles Gairdner Hospital
      • Waratah, Australia, 2298
        • Recruiting
        • Calvary Mater Newcastle
  • Brazil
      • Curitiba, Brazil, 81520-060
        • Recruiting
        • Liga Paranaense de Combate ao Câncer - Hospital Erasto Gaertner
      • São Paulo, Brazil, 05652-900
        • Recruiting
        • Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
      • São Paulo, Brazil, 05403-010
        • Recruiting
        • Hospital das Clínicas da Faculdade de Medicina da USP
      • São Paulo, Brazil, 01321-001
        • Recruiting
        • Real E Benemérita Associação Portuguesa de São Paulo
      • São Paulo, Brazil, 20231-050
        • Not yet recruiting
        • Instituto Nacional do Câncer
      • São Paulo, Brazil, 01308-070
        • Recruiting
        • Centro de Pesquisa Clínica - Hospital Nove de Julho
      • São Paulo, Brazil, 08270-120
        • Recruiting
        • Casa de Saúde Santa Marcelina
      • São Paulo, Brazil, 17210-190
        • Recruiting
        • Centro de Pesquisas Clínicas da Fundação Doutor Amaral Carvalho
  • France
      • Nantes, France, 44093
        • Recruiting
        • Chu Nantes-Hotel Dieu
      • Nice, France, 062000
        • Recruiting
        • Chu de Nice - Hôpital L'Archet 1
      • Paris, France, 75010
        • Recruiting
        • Hopital Saint Louis
      • Pessac, France, 33600
        • Recruiting
        • Chu Bordeaux, Hopital Du Haut Leveque
      • Toulouse, France, 31059
        • Recruiting
        • Institut Universitaire Du Cancer Toulouse-Oncopole
      • Vandœuvre-lès-Nancy, France, 54500
        • Recruiting
        • Chu Brabois
  • Germany
      • Dresden, Germany, 01307
        • Recruiting
        • Universitatsklinikum Dresden Carl Gustav Carus
      • Düsseldorf, Germany, 40477
        • Recruiting
        • Marien Hospital Duesseldorf
      • Göttingen, Germany, 37075
        • Recruiting
        • Universitaetsmedizin Goettingen (Umg)
      • Leipzig, Germany, 04103
        • Recruiting
        • Universitaetsklinikum Leipzig
      • Munich, Germany, 81675
        • Recruiting
        • Tum Klinikum Rechts Der Isar
  • Italy
      • Ancona, Italy, 60126
        • Recruiting
        • Azienda Ospedaliero Universitaria delle Marche
      • Bologna, Italy, 40138
        • Recruiting
        • Istituto Di Ematologia "Lorenzo E Ariosto Seragnoli" - Policlinico Di S. Orsola
      • Florence, Italy, 50139
        • Recruiting
        • Azienda Ospedaliero-Universitaria Careggi
      • Milan, Italy, 20089
        • Recruiting
        • Humanitas Research Hospital (Istituto Clinico Humanitas)
      • Pavia, Italy, 27100
        • Recruiting
        • Fondazione I.R.C.C.S. Policlinico San Matteo
      • Roma, Italy, 00133
        • Recruiting
        • Dipartimento Di Biomedicina E Prevenzione - Universita Degli Studi Di Roma "Tor Vergata"
      • Torino, Italy, 10126
        • Recruiting
        • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino - Presidio Molinette
  • Japan
      • Higashi-ku, Fukuoka-city, Fukuoka, Japan, 8128582
        • Recruiting
        • Kyushu University Hospital
      • Himeji-city, Hyogo, Japan, 6708540
        • Recruiting
        • Japanese Red Cross Society Himeji Hospital
      • Isehara-city, Kanagawa, Japan, 2591193
        • Recruiting
        • Tokai University Hospital
      • Musashino-city, Tokyo, Japan, 1808610
        • Recruiting
        • Japanese Red Cross Musashino Hospital
      • Sagamihara, Japan, 252-0375
        • Not yet recruiting
        • Kitasato University Hospital
    • Eiheiji-cho 670-8540 Himeji
      • Yoshida-gun, Eiheiji-cho 670-8540 Himeji, Japan, 910-1193
        • Recruiting
        • University of Fukui Hospital
  • Netherlands
      • Amsterdam, Netherlands, 1081HV
        • Recruiting
        • Umc Amsterdam - Vumc
      • Groningen, Netherlands, 9713GZ
        • Recruiting
        • Umc Groningen
  • Spain
      • Badalona, Spain, 8916
        • Recruiting
        • Institut Catala D' Oncologia
      • Barcelona, Spain, 8035
        • Recruiting
        • H. Valle de Hebron
      • Madrid, Spain, 28027
        • Recruiting
        • Clinica Universitaria de Navarra (Madrid)
      • Pamplona, Spain, 31008
        • Recruiting
        • Clinica Universitaria de Navarra (Pamplona)
      • Salamanca, Spain, 37007
        • Recruiting
        • Hospital Clinico Universitario de Salamanca
      • Seville, Spain, 41009
        • Recruiting
        • Hospital Universitario Virgen de la Macarena
      • Valencia, Spain, 46026
        • Recruiting
        • H. Universitario La Fe
  • United Kingdom
      • Edinburgh, United Kingdom, EH4 2XU
        • Recruiting
        • Western General Hospital
      • Leeds, United Kingdom, LS9 7TF
        • Withdrawn
        • St James' University Hospital
      • London, United Kingdom
        • Recruiting
        • Kings College Hospital
      • London, United Kingdom, NW1 2PG
        • Recruiting
        • University College London Hospital
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • Churchill Hospital
      • Torquay, United Kingdom, TQ2 7AA
        • Recruiting
        • Torbay Hospital
  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • Recruiting
        • Presbyterian / St. Luke'S Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago, Duchossois Center for Advanced Medicine (DCAM)
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • MSKCC
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • Recruiting
        • UNC Lineberger Comprehensive Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Oncology Associates of Oregon
    • Texas
      • Dallas, Texas, United States, 75235
        • Recruiting
        • University of Texas UT Southwestern Comprehensive Cancer Center
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ivosidenib monotherapy
Drug: 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.
Experimental: Azacitidine monotherapy
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants achieving CR and PR by 4 months
Time Frame: Through 4 months after starting treatment
Complete remission (CR) or Partial remission (PR) as per International Working Group (IWG) 2006 criteria
Through 4 months after starting treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response (OR) rate per IWG 2023 criteria
Time Frame: Through the end of the study (approximately 4 years)
Defined as CR (or CR equivalent) + PR + CRL + CRh + hematological improvement (HI)
Through the end of the study (approximately 4 years)
Event-free survival (EFS)
Time Frame: Through the end of the study (approximately 4 years)
Defined as the date of randomization to the date of first documented confirmed relapse /progression /death, whichever occurs first
Through the end of the study (approximately 4 years)
Overall Survival (OS)
Time Frame: Through the end of the study (approximately 4 years)
Defined as the time from randomization to the date of death due to any cause. Participants who are alive at the analysis cutoff date will be censored at the date they were last known to be alive.
Through the end of the study (approximately 4 years)
Duration of CR and PR
Time Frame: Through the end of the study (approximately 4 years)
Among participants who achieved CR+PR per IWG 2006 criteria
Through the end of the study (approximately 4 years)
Time to CR and PR
Time Frame: Through the end of the study (approximately 4 years)
Defined as time from the date of the randomization to the date of CR+PR, among participants who achieve CR+PR based on IWG 2006 Response Criteria
Through the end of the study (approximately 4 years)
Acute myeloid leukemia (AML) transformation rate
Time Frame: Through the end of the study (approximately 4 years)
Through the end of the study (approximately 4 years)
Time to transfusion independence (TTTI)
Time Frame: Through the end of the study (approximately 4 years)
Defined as time from date of randomization to date transfusion independence (TI) is first observed (Day 1 of a ≥ 56 days period without a transfusion), among participants who are baseline transfusion dependent and have achieved post-baseline TI. In the event a participant had more than one ≥ 56-day period, which met TI criteria, the earliest period will be used in analysis.
Through the end of the study (approximately 4 years)
Duration of transfusion independence (DOTI)
Time Frame: Through the end of the study (approximately 4 years)
Among participants who have achieved post-baseline TI, DOTI will be calculated as the time from the date TI is first observed (Day 1 of a ≥ 56-day period without a transfusion) until the day before the participants had a subsequent transfusion.
Through the end of the study (approximately 4 years)
Transfusion independence rate
Time Frame: Through the end of the study (approximately 4 years)
Through the end of the study (approximately 4 years)
Change from baseline in Quality of life (QOL) based on the QUALMS score
Time Frame: Through the Event Free Survival Follow up (approximately 4 years)
Quality of Life in Myelodysplasia Scale (QUALMS) scores range from 0 to 100, with a higher score representing a better QOL.
Through the Event Free Survival Follow up (approximately 4 years)
Change from baseline in health economic outcomes measures based on EQ-5D-5L score
Time Frame: Through the Event Free Survival Follow up (approximately 4 years)
Health economic outcomes measures as assessed by the 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) scores range from 5 to 25 with a higher number representing a worse health status.
Through the Event Free Survival Follow up (approximately 4 years)
Number of participants who proceed to hematopoietic stem cell transplantation (HSCT)
Time Frame: Through the end of the study (approximately 4 years)
Through the end of the study (approximately 4 years)
Ivosidenib plasma concentrations
Time Frame: Through Cycle 22 (each cycle is 28 days)
For participants receiving ivosidenib monotherapy
Through Cycle 22 (each cycle is 28 days)
2-HG plasma concentrations
Time Frame: Through Cycle 22 (each cycle is 28 days)
For participants receiving ivosidenib monotherapy
Through Cycle 22 (each cycle is 28 days)
Number of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment)
Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment)
Number of participants achieving CR and PR by 6 months as per IWG 2006 criteria
Time Frame: Through 6 months after starting treatment
Through 6 months after starting treatment
Number of participants achieving CR and PR by 6 months as per IWG 2023 criteria
Time Frame: Through 6 months after starting treatment
Through 6 months after starting treatment
Number of participants achieving CR and PR by 4 months as per IWG 2023 criteria
Time Frame: Through 4 months after starting treatment
Through 4 months after starting treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Institut de Recherches Internationales Servier

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Servier Bio-Innovation LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 3, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 14, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 20, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • S095031-178
  • 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation)
  • 2023-510155-37 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies:

  • used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

  • sponsored by Servier
  • with a first patient enrolled as of 1 January 2004 onwards
  • for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

IPD Sharing Time Frame

After Marketing Authorization in EEA or US if the study is used for the approval.

IPD Sharing Access Criteria

Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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