Clinical trial • Phase III • Haematology
IVOSIDENIB for Myelodysplastic syndrome | HMA-naive myelodysplastic syndrome
Phase III trial of IVOSIDENIB for Myelodysplastic syndrome | HMA-naive myelodysplastic syndrome.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- Myelodysplastic syndrome | HMA-naive myelodysplastic syndrome
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 14-08-2024
- First CTIS Authorization Date
- 02-12-2024
Trial design
Randomised, open-label, ivosidenib monotherapy: 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. | azacitidine monotherapy: 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.-controlled Phase III trial across 28 sites in France, Netherlands, Spain and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Ivosidenib monotherapy: 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. | Azacitidine monotherapy: 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.
- Target Sample Size
- 22
Eligibility
Recruits 22 Vulnerable population selected; no explicit details on consent or assent handling present in the provided content..
- Vulnerable Population
- Vulnerable population selected; no explicit details on consent or assent handling present in the provided content.
Inclusion criteria
- {"criterion_text":"- Diagnosis of HMA naive IDH1 R132 mutated MDS defined according to World Health Organization (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: o Have cytopenias related to MDS, defined as: <100 platelets/μL, or absolute neutrophil count (ANC) <1000/mm3, or Hgb <10g/dL AND o Have a blast count between 5-19% AND o Be eligible for HMA therapy (very low risk participants are to be excluded)."}
- {"criterion_text":"- Locally or centrally confirmed IDH1 R132 C/G/H/L/S mutation."}
Exclusion criteria
- {"criterion_text":"- 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."}
- {"criterion_text":"- > 20% blasts by morphology or immunohistochemistry on screening bone marrow aspirate."}
Endpoints
Primary endpoints
- {"endpoint_text":"- Complete remission (CR) + Partial remission (PR) by 4 months as per IWG 2006 criteria.","definition_or_measurement_approach":"Complete remission (CR) + Partial remission (PR) by 4 months assessed per IWG 2006 criteria."}
Secondary endpoints
- {"endpoint_text":"- Overall Response (OR) rate per IWG 2023 criteria defined as CR (or CR equivalent) + PR + CRL + CRh + hematological improvement (HI).","definition_or_measurement_approach":"Defined as CR (or CR equivalent) + PR + CRL + CRh + hematological improvement (HI) per IWG 2023 criteria."}
- {"endpoint_text":"- Event-free survival (EFS) defined as the date of randomization to the date of first documented confirmed relapse/progression/death, whichever occurs first.","definition_or_measurement_approach":"EFS measured from randomization to first documented confirmed relapse, progression, or death (whichever occurs first)."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"OS measured from randomization to date of death from any cause; surviving participants censored at last known alive date."}
- {"endpoint_text":"- Duration of CR and PR among participants who achieve CR + PR per IWG 2006 criteria.","definition_or_measurement_approach":"Duration measured among participants achieving CR or PR per IWG 2006 criteria."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time measured from randomization to date when CR or PR first observed per IWG 2006 Response Criteria."}
- {"endpoint_text":"- Acute myeloid leukemia (AML) transformation rate","definition_or_measurement_approach":"Rate of transformation to AML as documented during follow-up."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"TTTI measured from randomization to first day of a ≥56-day transfusion-free period among baseline transfusion-dependent participants who achieve TI; earliest qualifying period used if multiple."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"DOTI measured from first day of qualifying ≥56-day transfusion-free period until day before next transfusion."}
- {"endpoint_text":"- Transfusion independence rate","definition_or_measurement_approach":"Proportion of participants achieving transfusion independence as defined in protocol (≥56 days without transfusion)."}
- {"endpoint_text":"- Quality of Life in Myelodysplasia Scale (QUALMS) scores range from 0 to 100, with a higher score representing a better QOL.","definition_or_measurement_approach":"Measured by QUALMS; scores 0–100, higher indicates better quality of life."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured by EQ-5D-5L; scores 5–25, higher worse health status; analysis is change from baseline."}
- {"endpoint_text":"- Number of participants who proceed to hematopoietic stem cell transplantation (HSCT).","definition_or_measurement_approach":"Count of participants undergoing HSCT during study follow-up."}
- {"endpoint_text":"- Ivosidenib plasma concentration and 2-HG plasma concentrations for participants receiving Ivosidenib monotherapy.","definition_or_measurement_approach":"Plasma concentrations of ivosidenib and 2-HG measured per PK/PD schedule for participants on ivosidenib monotherapy."}
- {"endpoint_text":"- Number of participants achieving CR and PR by 6 months as per IWG 2006 criteria.","definition_or_measurement_approach":"Count of participants achieving CR or PR within 6 months assessed by IWG 2006 criteria."}
- {"endpoint_text":"- Number of participants achieving CR and PR by 6 months as per IWG 2023 criteria.","definition_or_measurement_approach":"Count of participants achieving CR or PR within 6 months assessed by IWG 2023 criteria."}
- {"endpoint_text":"- Number of participants achieving CR and PR by 4 months as per IWG 2023 criteria.","definition_or_measurement_approach":"Count of participants achieving CR or PR within 4 months assessed by IWG 2023 criteria."}
- {"endpoint_text":"- Number of adverse events (AEs) and serious adverse events (SAEs).","definition_or_measurement_approach":"Counts of AEs and SAEs reported per standard definitions and reporting windows."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"EQ-5D-5L scores (5–25) used as health economic outcomes; higher scores indicate worse health status; measured per protocol schedule."}
Recruitment
- Planned Sample Size
- 22
- Recruitment Window Months
- 47
- Consent Approach
- Informed consent obtained using subject information sheets and informed consent forms (SIS and ICF). Documents available in multiple languages including French, Spanish, Italian, German, Dutch and English. Consent to be provided by adult participants. No explicit details on assent procedures for minors provided in the available content.
Geography
- Total Number Of Sites
- 28
- Total Number Of Participants
- 26
France
- Earliest CTIS Part Ii Submission Date
- 26-09-2024
- Latest Decision Or Authorization Date
- 27-04-2026
- Processing Time Days
- 578
- Number Of Sites
- 6
- Number Of Participants
- 5
Sites
- Site Name
- CHRU De Nancy
- Department Name
- Service d'hématologie clinique
- Principal Investigator Name
- Maud D'AVENI-PINEY
- Principal Investigator Email
- m.daveni-piney@chru-nancy.fr
- Contact Person Name
- Maud D'AVENI-PINEY
- Contact Person Email
- m.daveni-piney@chru-nancy.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Service d’hématologie sénior
- Principal Investigator Name
- Marie SEBERT
- Principal Investigator Email
- marie.sebert@aphp.fr
- Contact Person Name
- Marie SEBERT
- Contact Person Email
- marie.sebert@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Nice
- Department Name
- Service d’hématologie clinique
- Principal Investigator Name
- Thomas CLUZEAU
- Principal Investigator Email
- cluzeau.t@chu-nice.fr
- Contact Person Name
- Thomas CLUZEAU
- Contact Person Email
- cluzeau.t@chu-nice.fr
- Site Name
- Centre Hospitalier Universitaire De Nantes
- Department Name
- Service hématologie clinique
- Principal Investigator Name
- Alice GARNIER
- Principal Investigator Email
- alice.garnier@chu-nantes.fr
- Contact Person Name
- Alice GARNIER
- Contact Person Email
- alice.garnier@chu-nantes.fr
- Site Name
- Centre Hospitalier Universitaire De Toulouse
- Department Name
- Service de médecine interne et immunopathologie
- Principal Investigator Name
- Thibault COMONT
- Principal Investigator Email
- comont.thibault@iuct-oncopole.fr
- Contact Person Name
- Thibault COMONT
- Contact Person Email
- comont.thibault@iuct-oncopole.fr
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Department Name
- Service d'hématologie clinique et thérapie cellulaire
- Principal Investigator Name
- Sophie DIMICOLI-SALAZAR
- Principal Investigator Email
- sophie.dimicoli-salazar@chu-bordeaux.fr
- Contact Person Name
- Sophie DIMICOLI-SALAZAR
- Contact Person Email
- sophie.dimicoli-salazar@chu-bordeaux.fr
Netherlands
- Earliest CTIS Part Ii Submission Date
- 08-11-2024
- Latest Decision Or Authorization Date
- 28-04-2026
- Processing Time Days
- 536
- Number Of Sites
- 2
- Number Of Participants
- 2
Sites
- Site Name
- Amsterdam UMC Stichting
- Department Name
- Hematology
- Principal Investigator Name
- Canan Alhan
- Principal Investigator Email
- hematology@amsterdamumc.nl
- Contact Person Name
- Canan Alhan
- Contact Person Email
- hematology@amsterdamumc.nl
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Hematology
- Principal Investigator Name
- Gerwin Huls
- Principal Investigator Email
- g.huls@umcg.nl
- Contact Person Name
- Gerwin Huls
- Contact Person Email
- g.huls@umcg.nl
Spain
- Earliest CTIS Part Ii Submission Date
- 07-11-2024
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 539
- Number Of Sites
- 7
- Number Of Participants
- 6
Sites
- Site Name
- Vall D Hebron Institute Of Oncology
- Department Name
- Hematology
- Principal Investigator Name
- David Valcarcel Ferreiras
- Principal Investigator Email
- dvalcarcel@vhio.net
- Contact Person Name
- David Valcarcel Ferreiras
- Contact Person Email
- dvalcarcel@vhio.net
- Site Name
- Clinica Universidad De Navarra
- Department Name
- Hematology
- Principal Investigator Name
- Ana Alonso
- Principal Investigator Email
- aalfonso@unav.es
- Contact Person Name
- Ana Alonso
- Contact Person Email
- aalfonso@unav.es
- Site Name
- Hospital Universitario De Salamanca
- Department Name
- Hematology
- Principal Investigator Name
- María Diez Campelo
- Principal Investigator Email
- mdiezcampelo@usal.es
- Contact Person Name
- María Diez Campelo
- Contact Person Email
- mdiezcampelo@usal.es
- Site Name
- Hospital Universitario Virgen De La Macarena
- Department Name
- Hematology
- Principal Investigator Name
- Ildefonso Espigado Tocino
- Principal Investigator Email
- espigado@us.es
- Contact Person Name
- Ildefonso Espigado Tocino
- Contact Person Email
- espigado@us.es
- Site Name
- Institut Catala D'oncologia
- Department Name
- Hematology
- Principal Investigator Name
- Blanca Xicoy Cirici
- Principal Investigator Email
- bxicoy@iconcologia.net
- Contact Person Name
- Blanca Xicoy Cirici
- Contact Person Email
- bxicoy@iconcologia.net
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- Hematology
- Principal Investigator Name
- Evelyn Acuña Cruz
- Principal Investigator Email
- evelyn_acuna@islafe.es
- Contact Person Name
- Evelyn Acuña Cruz
- Contact Person Email
- evelyn_acuna@islafe.es
- Site Name
- Clinica Universidad De Navarra
- Department Name
- Hematology
- Principal Investigator Name
- Ana Alonso
- Principal Investigator Email
- aalfonso@unav.es
- Contact Person Name
- Ana Alonso
- Contact Person Email
- aalfonso@unav.es
Germany
- Earliest CTIS Part Ii Submission Date
- 27-11-2024
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 519
- Number Of Sites
- 6
- Number Of Participants
- 5
Sites
- Site Name
- Universitaet Leipzig
- Department Name
- Klinik und Poliklinik für Hämatologie, Zelltherapie, Hämostaseologie und Intektiologie
- Principal Investigator Name
- Dominic Brauer
- Principal Investigator Email
- Dominic.Brauer@medizin.uni-leipzig.de
- Contact Person Name
- Dominic Brauer
- Contact Person Email
- Dominic.Brauer@medizin.uni-leipzig.de
- Site Name
- Technische Universitaet Dresden
- Department Name
- Medizinische Fakultät Carl Gustav Carus, Medizinische Klinik und Poliklinik I
- Principal Investigator Name
- Katja Sockel
- Principal Investigator Email
- Katja.Sockel@ukdd.de
- Contact Person Name
- Katja Sockel
- Contact Person Email
- Katja.Sockel@ukdd.de
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- Medizinische Klinik - Hämatologie und Internistische Onkologie
- Principal Investigator Name
- Katharina Götze
- Principal Investigator Email
- katharina.goetze@mri.tum.de
- Contact Person Name
- Katharina Götze
- Contact Person Email
- katharina.goetze@mri.tum.de
- Site Name
- Universitaetsmedizin Goettingen
- Department Name
- Klinik für Hämatologie und Medizinische Onkologie
- Principal Investigator Name
- Hannes Treiber
- Principal Investigator Email
- sz-umg.sponsor-qm@med.uni-goettingen.de
- Contact Person Name
- Hannes Treiber
- Contact Person Email
- sz-umg.sponsor-qm@med.uni-goettingen.de
- Site Name
- Marien Hospital Duesseldorf GmbH
- Department Name
- Klinik für Onkologie, Hämatologie und Palliativmedizin
- Principal Investigator Name
- Aristoteles Giagounidis
- Principal Investigator Email
- aristoteles.giagounidis@vkkd-kliniken.de
- Contact Person Name
- Aristoteles Giagounidis
- Contact Person Email
- aristoteles.giagounidis@vkkd-kliniken.de
- Site Name
- Medizinische Hochschule Hannover
- Department Name
- Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
- Principal Investigator Name
- Felicitas Thol
- Principal Investigator Email
- Thol.Felicitas@mh-hannover.de
- Contact Person Name
- Felicitas Thol
- Contact Person Email
- Thol.Felicitas@mh-hannover.de
Italy
- Earliest CTIS Part Ii Submission Date
- 05-11-2024
- Latest Decision Or Authorization Date
- 30-04-2026
- Processing Time Days
- 541
- Number Of Sites
- 7
- Number Of Participants
- 8
Sites
- Site Name
- Humanitas Mirasole S.p.A.
- Department Name
- Sezione Leucemie e Mielodisplasie
- Principal Investigator Name
- Matteo Giovanni Della Porta
- Principal Investigator Email
- matteo.della_porta@hunimed.eu
- Contact Person Name
- Matteo Giovanni Della Porta
- Contact Person Email
- matteo.della_porta@hunimed.eu
- Site Name
- Careggi University Hospital
- Department Name
- SOD Ematologia
- Principal Investigator Name
- Valeria Santini
- Principal Investigator Email
- valeria.santini@unifi.it
- Contact Person Name
- Valeria Santini
- Contact Person Email
- valeria.santini@unifi.it
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- Dipartimento di Oncologia
- Principal Investigator Name
- Chiara Frairia
- Principal Investigator Email
- cfrairia@cittadellasalute.to.it
- Contact Person Name
- Chiara Frairia
- Contact Person Email
- cfrairia@cittadellasalute.to.it
- Site Name
- Fondazione IRCCS Policlinico San Matteo
- Department Name
- Dipartimento di Oncologia
- Principal Investigator Name
- Luca Malcovati
- Principal Investigator Email
- l.malcovati@smatteo.pv.it
- Contact Person Name
- Luca Malcovati
- Contact Person Email
- l.malcovati@smatteo.pv.it
- Site Name
- Azienda Ospedaliero Universitaria Delle Marche
- Department Name
- SOD Clinica Ematologica
- Principal Investigator Name
- Antonella Poloni
- Principal Investigator Email
- a.poloni@staff.univpm.it
- Contact Person Name
- Antonella Poloni
- Contact Person Email
- a.poloni@staff.univpm.it
- Site Name
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Department Name
- U.O. di Ematologia
- Principal Investigator Name
- Stefania Paolini
- Principal Investigator Email
- stefania.paolini@unibo.it
- Contact Person Name
- Stefania Paolini
- Contact Person Email
- stefania.paolini@unibo.it
- Site Name
- Universita' Degli Studi Di Roma Tor Vergata
- Department Name
- Dipartimento di Biomedicina e Prevenzione
- Principal Investigator Name
- Maria Teresa Voso
- Principal Investigator Email
- voso@med.uniroma2.it
- Contact Person Name
- Maria Teresa Voso
- Contact Person Email
- voso@med.uniroma2.it
Sponsor
Primary sponsor
- Full Name
- Institut De Recherches Internationales Servier IRIS
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- France
Third parties
- {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long Term Storage / Biobank","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central Lab / Logistic platform","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Kayentis","duties_or_roles":"eCOA","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Cenetron Diagnostics Ltd.","duties_or_roles":"IDH1 mutation assessment","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Tempus AI Inc.","duties_or_roles":"IPSS-M calculation","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Hematogenix Laboratory Services Limited","duties_or_roles":"MRD by flow cytometry","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"PK/PD, 2-HG and study drug in plasma","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient payment & reimbursement services","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United States","full_name":"Hematogenix Laboratory Services LLC","duties_or_roles":"Molecular analysis, including NGS for IPSS-M","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"Support functions (role code 1)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- AG-120/S95031 250mg film-coated tablet
- Active Substance
- IVOSIDENIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- Investigational product (no marketing authorisation listed in provided data)
- Starting Dose
- 500 mg orally once daily (two 250 mg tablets)
- Dose Levels
- 500 mg once daily
- Frequency
- Once daily
- Maximum Dose
- 500 mg daily
- Investigational Product Name
- Vidaza 25 mg/ml powder for suspension for injection
- Active Substance
- AZACITIDINE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS (IV) OR SUBCUTANEOUS (SC)
- Route
- SC or IV
- Authorisation Status
- Authorised medicine (marketing authorisation EU/1/08/488/001)
- Starting Dose
- 75 mg/m^2/day administered by SC or IV for 7 days of each 28-day cycle
- Dose Levels
- 75 mg/m^2/day for 7 days per 28-day cycle
- Frequency
- Daily for 7 days of each 28-day cycle
- Maximum Dose
- 75 mg/m^2 per day
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