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.
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
- Conditions the study is for
- Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS), Myelodysplastic Syndromes (MDS)
- What is being tested?
- Ivosidenib and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- 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
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
62 sites in 10 countries
United States9 sites, 9 recruiting
- 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
Brazil8 sites, 8 recruiting
- 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
- Not yet recruiting
Instituto Nacional do Câncer
São Paulo, 20231-050
Italy7 sites, 7 recruiting
- 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
Spain7 sites, 7 recruiting
- 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
Australia6 sites, 6 recruiting
- Not yet recruiting
Royal Adelaide Hospital
Adelaide, 5000
- Recruiting
Monash Health
Clayton, 3168
- Recruiting
Northern Health
Epping, 3076
- Not yet recruiting
Liverpool Hospital
Liverpool, 2170
- Recruiting
Sir Charles Gairdner Hospital
Nedlands, 6009
- Recruiting
Calvary Mater Newcastle
Waratah, 2298
France6 sites, 6 recruiting
- 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
Japan6 sites, 6 recruiting
- 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
- Not yet recruiting
Kitasato University Hospital
Sagamihara, 252-0375
- Recruiting
University of Fukui Hospital
Yoshida-gun, Eiheiji-cho 670-8540 Himeji, 910-1193
United Kingdom6 sites, 5 recruiting
- Recruiting
Western General Hospital
Edinburgh, EH4 2XU
- Withdrawn
St James' University Hospital
Leeds, LS9 7TF
- Recruiting
University College London Hospital
London, NW1 2PG
- Recruiting
Kings College Hospital
London
- Recruiting
Churchill Hospital
Oxford, OX3 7LE
- Recruiting
Torbay Hospital
Torquay, TQ2 7AA
Germany5 sites, 5 recruiting
- 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
Netherlands2 sites, 2 recruiting
- Recruiting
Umc Amsterdam - Vumc
Amsterdam, 1081HV
- Recruiting
Umc Groningen
Groningen, 9713GZ
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.
- Conditions
- Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS), Myelodysplastic Syndromes (MDS)
- 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 group | Role | What they receive |
|---|---|---|
| Ivosidenib monotherapy | Experimental | Not described Receives: Drug: Ivosidenib |
| Azacitidine monotherapy | Experimental | Not described Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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)
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)
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)
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)
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)
Acute myeloid leukemia (AML) transformation rate
Measured: Through the end of the study (approximately 4 years)
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)
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)
Transfusion independence rate
Measured: Through the end of the study (approximately 4 years)
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)
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)
Number of participants who proceed to hematopoietic stem cell transplantation (HSCT)
Measured: Through the end of the study (approximately 4 years)
Ivosidenib plasma concentrations
For participants receiving ivosidenib monotherapy
Measured: Through Cycle 22 (each cycle is 28 days)
2-HG plasma concentrations
For participants receiving ivosidenib monotherapy
Measured: Through Cycle 22 (each cycle is 28 days)
Number of participants achieving CR and PR by 6 months as per IWG 2006 criteria
Measured: Through 6 months after starting treatment
Number of participants achieving CR and PR by 6 months as per IWG 2023 criteria
Measured: Through 6 months after starting treatment
Number of participants achieving CR and PR by 4 months as per IWG 2023 criteria
Measured: Through 4 months after starting treatment
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.
- First posted20 Jun 2024
- Study start3 Dec 2024
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Institut de Recherches Internationales Servier
- Sponsor type
- University, hospital or other
- Collaborators
- Servier Bio-Innovation LLC
- Responsible party
- Sponsor
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.