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Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS)Phase 3PyramIDHNCT06465953

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

A Phase 3 study testing Ivosidenib and Azacitidine in people with Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) and Myelodysplastic Syndromes (MDS), run by Institut de Recherches Internationales Servier at 62 sites in 10 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ivosidenib and Azacitidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
62 sitesin 10 countries
Study dates
3 Dec 2024to 1 Dec 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

62 sites in 10 countries. Contact the study team or a site near you to ask about taking part.

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

+33 1 55 72 60 00

scientificinformation@servier.com

62 sites in 10 countries

United States9 sites, 9 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Andrew Brunner, 617-724-1124, abrunner@mgb.org

    Recruiting

  • Unc Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27514

    Recruiting

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

    Chicago, Illinois, 60637

    Recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    Recruiting

  • University of Texas UT Southwestern Comprehensive Cancer Center

    Dallas, Texas, 75235

    Recruiting

  • Presbyterian / St. Luke'S Medical Center

    Denver, Colorado, 80218

    Recruiting

  • Oncology Associates of Oregon

    Eugene, Oregon, 97401

    Recruiting

  • MD Anderson Cancer Centre

    Houston, Texas, 77030

    Recruiting

  • MSKCC

    New York, New York, 10065

    Recruiting

Other trials in United States

Brazil8 sites, 8 recruiting

  • Liga Paranaense de Combate ao Câncer - Hospital Erasto Gaertner

    Curitiba, 81520-060

    Recruiting

  • Centro de Pesquisa Clínica - Hospital Nove de Julho

    São Paulo, 01308-070

    Recruiting

  • Real E Benemérita Associação Portuguesa de São Paulo

    São Paulo, 01321-001

    Recruiting

  • Hospital das Clínicas da Faculdade de Medicina da USP

    São Paulo, 05403-010

    Recruiting

  • Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein

    São Paulo, 05652-900

    Recruiting

  • Casa de Saúde Santa Marcelina

    São Paulo, 08270-120

    Recruiting

  • Centro de Pesquisas Clínicas da Fundação Doutor Amaral Carvalho

    São Paulo, 17210-190

    Recruiting

  • Instituto Nacional do Câncer

    São Paulo, 20231-050

    Not yet recruiting

Other trials in Brazil

Italy7 sites, 7 recruiting

  • Azienda Ospedaliero Universitaria Delle Marche

    Ancona, 60126

    Recruiting

  • Istituto Di Ematologia "Lorenzo E Ariosto Seragnoli" - Policlinico Di S. Orsola

    Bologna, 40138

    Recruiting

  • Azienda Ospedaliero-Universitaria Careggi

    Florence, 50139

    Recruiting

  • Humanitas Research Hospital (Istituto Clinico Humanitas)

    Milan, 20089

    Recruiting

  • Fondazione I.R.C.C.S. Policlinico San Matteo

    Pavia, 27100

    Recruiting

  • Dipartimento Di Biomedicina E Prevenzione - Universita Degli Studi Di Roma "Tor Vergata"

    Roma, 00133

    Recruiting

  • Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino - Presidio Molinette

    Torino, 10126

    Recruiting

Other trials in Italy

Spain7 sites, 7 recruiting

  • Institut Catala D' Oncologia

    Badalona, 8916

    Recruiting

  • H. Valle de Hebron

    Barcelona, 8035

    Recruiting

  • Clinica Universitaria de Navarra (Madrid)

    Madrid, 28027

    Recruiting

  • Clinica Universitaria de Navarra (Pamplona)

    Pamplona, 31008

    Recruiting

  • Hospital Clinico Universitario de Salamanca

    Salamanca, 37007

    Recruiting

  • Hospital Universitario Virgen de La Macarena

    Seville, 41009

    Recruiting

  • H. Universitario La Fe

    Valencia, 46026

    Recruiting

Other trials in Spain

Australia6 sites, 6 recruiting

  • Royal Adelaide Hospital

    Adelaide, 5000

    Not yet recruiting

  • Monash Health

    Clayton, 3168

    Recruiting

  • Northern Health

    Epping, 3076

    Recruiting

  • Liverpool Hospital

    Liverpool, 2170

    Not yet recruiting

  • Sir Charles Gairdner Hospital

    Nedlands, 6009

    Recruiting

  • Calvary Mater Newcastle

    Waratah, 2298

    Recruiting

Other trials in Australia

France6 sites, 6 recruiting

  • Chu Nantes-Hotel Dieu

    Nantes, 44093

    Recruiting

  • Chu de Nice - Hôpital L'Archet 1

    Nice, 062000

    Recruiting

  • Hopital Saint Louis

    Paris, 75010

    Recruiting

  • Chu Bordeaux, Hopital Du Haut Leveque

    Pessac, 33600

    Recruiting

  • Institut Universitaire Du Cancer Toulouse-Oncopole

    Toulouse, 31059

    Recruiting

  • Chu Brabois

    Vandœuvre-lès-Nancy, 54500

    Recruiting

Other trials in France

Japan6 sites, 6 recruiting

  • Kyushu University Hospital

    Higashi-ku, Fukuoka-city, Fukuoka, 8128582

    Recruiting

  • Japanese Red Cross Society Himeji Hospital

    Himeji-city, Hyogo, 6708540

    Recruiting

  • Tokai University Hospital

    Isehara-city, Kanagawa, 2591193

    Recruiting

  • Japanese Red Cross Musashino Hospital

    Musashino-city, Tokyo, 1808610

    Recruiting

  • Kitasato University Hospital

    Sagamihara, 252-0375

    Not yet recruiting

  • University of Fukui Hospital

    Yoshida-gun, Eiheiji-cho 670-8540 Himeji, 910-1193

    Recruiting

Other trials in Japan

United Kingdom6 sites, 5 recruiting

  • Western General Hospital

    Edinburgh, EH4 2XU

    Recruiting

  • St James' University Hospital

    Leeds, LS9 7TF

    Withdrawn

  • University College London Hospital

    London, NW1 2PG

    Recruiting

  • Kings College Hospital

    London

    Recruiting

  • Churchill Hospital

    Oxford, OX3 7LE

    Recruiting

  • Torbay Hospital

    Torquay, TQ2 7AA

    Recruiting

Other trials in United Kingdom

Germany5 sites, 5 recruiting

  • Universitatsklinikum Dresden Carl Gustav Carus

    Dresden, 01307

    Recruiting

  • Marien Hospital Duesseldorf

    Düsseldorf, 40477

    Recruiting

  • Universitaetsmedizin Goettingen (Umg)

    Göttingen, 37075

    Recruiting

  • Universitaetsklinikum Leipzig

    Leipzig, 04103

    Recruiting

  • Tum Klinikum Rechts Der Isar

    Munich, 81675

    Recruiting

Other trials in Germany

Netherlands2 sites, 2 recruiting

  • Umc Amsterdam - Vumc

    Amsterdam, 1081HV

    Recruiting

  • Umc Groningen

    Groningen, 9713GZ

    Recruiting

Other trials in Netherlands

About this study

Official title: 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.

Being tested
Ivosidenib, Azacitidine
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvosidenibDrug

    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.

  • AzacitidineDrug

    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 groups in NCT06465953
Study groupRoleWhat they receive
Ivosidenib monotherapyExperimentalNot described
Receives: Drug: Ivosidenib
Azacitidine monotherapyExperimentalNot described
Receives: Drug: Azacitidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants achieving CR and PR by 4 months

    Complete remission (CR) or Partial remission (PR) as per International Working Group (IWG) 2006 criteria

    Measured: Through 4 months after starting treatment

Secondary outcomes (18)

  1. Overall Response (OR) rate per IWG 2023 criteria

    Defined as CR (or CR equivalent) + PR + CRL + CRh + hematological improvement (HI)

    Measured: Through the end of the study (approximately 4 years)

  2. Event-free survival (EFS)

    Defined as the date of randomization to the date of first documented confirmed relapse /progression /death, whichever occurs first

    Measured: Through the end of the study (approximately 4 years)

  3. Overall Survival (OS)

    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.

    Measured: Through the end of the study (approximately 4 years)

  4. Duration of CR and PR

    Among participants who achieved CR+PR per IWG 2006 criteria

    Measured: Through the end of the study (approximately 4 years)

  5. Time to CR and PR

    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

    Measured: Through the end of the study (approximately 4 years)

  6. Acute myeloid leukemia (AML) transformation rate

    Measured: Through the end of the study (approximately 4 years)

  7. Time to transfusion independence (TTTI)

    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.

    Measured: Through the end of the study (approximately 4 years)

  8. Duration of transfusion independence (DOTI)

    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.

    Measured: Through the end of the study (approximately 4 years)

  9. Transfusion independence rate

    Measured: Through the end of the study (approximately 4 years)

  10. Change from baseline in Quality of life (QOL) based on the QUALMS score

    Quality of Life in Myelodysplasia Scale (QUALMS) scores range from 0 to 100, with a higher score representing a better QOL.

    Measured: Through the Event Free Survival Follow up (approximately 4 years)

  11. Change from baseline in health economic outcomes measures based on EQ-5D-5L score

    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.

    Measured: Through the Event Free Survival Follow up (approximately 4 years)

  12. Number of participants who proceed to hematopoietic stem cell transplantation (HSCT)

    Measured: Through the end of the study (approximately 4 years)

  13. Ivosidenib plasma concentrations

    For participants receiving ivosidenib monotherapy

    Measured: Through Cycle 22 (each cycle is 28 days)

  14. 2-HG plasma concentrations

    For participants receiving ivosidenib monotherapy

    Measured: Through Cycle 22 (each cycle is 28 days)

  15. Number of participants achieving CR and PR by 6 months as per IWG 2006 criteria

    Measured: Through 6 months after starting treatment

  16. Number of participants achieving CR and PR by 6 months as per IWG 2023 criteria

    Measured: Through 6 months after starting treatment

  17. Number of participants achieving CR and PR by 4 months as per IWG 2023 criteria

    Measured: Through 4 months after starting treatment

  18. Number of adverse events (AEs) and serious adverse events (SAEs)

    Measured: Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2024
  2. Study start3 Dec 2024
  3. Primary completion1 Nov 2027 (estimated)
  4. Study completion1 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06465953
Sponsor's protocol ID
S095031-178
Other IDs
2023-510155-37, 2023
Acronym
PyramIDH
Status last verified
Sep 2026
First submitted
14 Jun 2024
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ivosidenib and Azacitidine in people with Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) and Myelodysplastic Syndromes (MDS), run by Institut de Recherches Internationales Servier at 62 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 62 sites in United States, Brazil, Italy, Spain, Australia and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department (+33 1 55 72 60 00, scientificinformation@servier.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants achieving CR and PR by 4 months (time frame: Through 4 months after starting treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06465953.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.

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