Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an IDH1 Mutation
PyramIDH
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)
2 other identifiers
interventional
48
10 countries
62
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Dec 2024
Typical duration for phase_3
62 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 14, 2024
CompletedFirst Posted
Study publicly available on registry
June 20, 2024
CompletedStudy Start
First participant enrolled
December 3, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
February 11, 2026
February 1, 2026
2.9 years
June 14, 2024
February 9, 2026
Conditions
Outcome Measures
Primary Outcomes (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
Through 4 months after starting treatment
Secondary Outcomes (18)
Overall Response (OR) rate per IWG 2023 criteria
Through the end of the study (approximately 4 years)
Event-free survival (EFS)
Through the end of the study (approximately 4 years)
Overall Survival (OS)
Through the end of the study (approximately 4 years)
Duration of CR and PR
Through the end of the study (approximately 4 years)
Time to CR and PR
Through the end of the study (approximately 4 years)
- +13 more secondary outcomes
Study Arms (2)
Ivosidenib monotherapy
EXPERIMENTALAzacitidine monotherapy
EXPERIMENTALInterventions
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 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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (62)
Presbyterian / St. Luke'S Medical Center
Denver, Colorado, 80218, United States
University of Chicago, Duchossois Center for Advanced Medicine (DCAM)
Chicago, Illinois, 60637, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
MSKCC
New York, New York, 10065, United States
Unc Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27514, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Oncology Associates of Oregon
Eugene, Oregon, 97401, United States
University of Texas UT Southwestern Comprehensive Cancer Center
Dallas, Texas, 75235, United States
MD Anderson Cancer Centre
Houston, Texas, 77030, United States
Royal Adelaide Hospital
Adelaide, 5000, Australia
Monash Health
Clayton, 3168, Australia
Northern Health
Epping, 3076, Australia
Liverpool Hospital
Liverpool, 2170, Australia
Sir Charles Gairdner Hospital
Nedlands, 6009, Australia
Calvary Mater Newcastle
Waratah, 2298, Australia
Liga Paranaense de Combate ao Câncer - Hospital Erasto Gaertner
Curitiba, 81520-060, Brazil
Centro de Pesquisa Clínica - Hospital Nove de Julho
São Paulo, 01308-070, Brazil
Real E Benemérita Associação Portuguesa de São Paulo
São Paulo, 01321-001, Brazil
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo, 05403-010, Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
São Paulo, 05652-900, Brazil
Casa de Saúde Santa Marcelina
São Paulo, 08270-120, Brazil
Centro de Pesquisas Clínicas da Fundação Doutor Amaral Carvalho
São Paulo, 17210-190, Brazil
Instituto Nacional do Câncer
São Paulo, 20231-050, Brazil
Chu Nantes-Hotel Dieu
Nantes, 44093, France
Chu de Nice - Hôpital L'Archet 1
Nice, 062000, France
Hopital Saint Louis
Paris, 75010, France
Chu Bordeaux, Hopital Du Haut Leveque
Pessac, 33600, France
Institut Universitaire Du Cancer Toulouse-Oncopole
Toulouse, 31059, France
Chu Brabois
Vandœuvre-lès-Nancy, 54500, France
Universitatsklinikum Dresden Carl Gustav Carus
Dresden, 01307, Germany
Marien Hospital Duesseldorf
Düsseldorf, 40477, Germany
Universitaetsmedizin Goettingen (Umg)
Göttingen, 37075, Germany
Universitaetsklinikum Leipzig
Leipzig, 04103, Germany
Tum Klinikum Rechts Der Isar
Munich, 81675, Germany
Azienda Ospedaliero Universitaria Delle Marche
Ancona, 60126, Italy
Istituto Di Ematologia "Lorenzo E Ariosto Seragnoli" - Policlinico Di S. Orsola
Bologna, 40138, Italy
Azienda Ospedaliero-Universitaria Careggi
Florence, 50139, Italy
Humanitas Research Hospital (Istituto Clinico Humanitas)
Milan, 20089, Italy
Fondazione I.R.C.C.S. Policlinico San Matteo
Pavia, 27100, Italy
Dipartimento Di Biomedicina E Prevenzione - Universita Degli Studi Di Roma "Tor Vergata"
Roma, 00133, Italy
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino - Presidio Molinette
Torino, 10126, Italy
University of Fukui Hospital
Yoshida-gun, Eiheiji-cho 670-8540 Himeji, 910-1193, Japan
Kyushu University Hospital
Higashi-ku, Fukuoka-city, Fukuoka, 8128582, Japan
Japanese Red Cross Society Himeji Hospital
Himeji-city, Hyogo, 6708540, Japan
Tokai University Hospital
Isehara-city, Kanagawa, 2591193, Japan
Japanese Red Cross Musashino Hospital
Musashino-city, Tokyo, 1808610, Japan
Kitasato University Hospital
Sagamihara, 252-0375, Japan
Umc Amsterdam - Vumc
Amsterdam, 1081HV, Netherlands
Umc Groningen
Groningen, 9713GZ, Netherlands
Institut Catala D' Oncologia
Badalona, 8916, Spain
H. Valle de Hebron
Barcelona, 8035, Spain
Clinica Universitaria de Navarra (Madrid)
Madrid, 28027, Spain
Clinica Universitaria de Navarra (Pamplona)
Pamplona, 31008, Spain
Hospital Clinico Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitario Virgen de La Macarena
Seville, 41009, Spain
H. Universitario La Fe
Valencia, 46026, Spain
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
St James' University Hospital
Leeds, LS9 7TF, United Kingdom
University College London Hospital
London, NW1 2PG, United Kingdom
Kings College Hospital
London, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Torbay Hospital
Torquay, TQ2 7AA, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 14, 2024
First Posted
June 20, 2024
Study Start
December 3, 2024
Primary Completion (Estimated)
November 1, 2027
Study Completion (Estimated)
December 1, 2028
Last Updated
February 11, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- After Marketing Authorization in EEA or US if the study is used for the approval.
- 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.
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.