An Open-label Phase 3b Study of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy.

A Single Arm, Open-label Phase 3b Study to Describe the Safety and Tolerability of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy

The purpose of this study is to learn more about the safety and efficacy of ivosidenib taken with azacitidine to treat adult patients with acute myeloid leukemia (AML) who are presenting a gene mutation called IDH1 (isocitrate dehydrogenase1 mutation-positive [IDH1m]) and cannot receive treatment with intensive chemotherapy (IC).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Ivosidenib 500mg Oral Tablet; Drug: Azacitidine

Detailed Description

Participants who are eligible and enroll in the study will attend a study visit on the first day of each 28-day cycle. Study visits will consist of a physical exam, blood work, electrocardiogram (ECG) and other assessments. After treatment discontinuation participants will be contacted every 12 weeks through the end of the study (currently planned for 2026) to assess survival. The study drug, Ivosidenib, will be taken once daily throughout the duration of participation in the study, and Azacitidine will only be administered for 7 days at the beginning of each 28 day cycle. If at any point ivosidenib is made available as a medical prescription at the patient's site, the patient will switch to commercial product and will continue to be followed according to the protocol.

• Study Type: Interventional
• Enrollment (Estimated): 245
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Servier Affaires Médicales; Phone Number: +33 1 55 72 60 00; Email: scientificinformation@servier.com

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Completed
    • AKH - Medizinische Universitat Wien
  • Wels, Austria, 4600
    • Completed
    • Klinikum Wels-Grieskirchen GmbH
• France
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13273
      • Recruiting
      • Institut Paoli Calmettes
  • Calvados
    • Caen, Calvados, France, 14033
      • Recruiting
      • Chu Caen - Hôpital de La Côte de Nacre
  • Haute Garonne
    • Toulouse, Haute Garonne, France, 31059
      • Recruiting
      • CHU de Toulouse pt
  • Ille Et Vilaine
    • Rennes, Ille Et Vilaine, France, 35033
      • Not yet recruiting
      • CHU Rennes - Hôpital Pontchaillou
  • Liore
    • Angers, Liore, France, 49100
      • Not yet recruiting
      • CHU Angers - Hopital Hotel Dieu
• Italy
  • Brescia, Italy, 25123
    • Recruiting
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)
  • Genova, Italy, 16132
    • Recruiting
    • IRCCS Ospedale Policlinico San Martino
  • Perugia, Italy, 06135
    • Recruiting
    • Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia
  • Forli-Cesena
    • Meldola, Forli-Cesena, Italy, 47014
      • Recruiting
      • IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST
• Netherlands
  • Amersfoort, Netherlands, 3818 AZ
    • Recruiting
    • Meander Medisch Centrum
  • Amsterdam, Netherlands, 1105 AZ
    • Recruiting
    • Amsterdam UMC
  • Arnhem, Netherlands, 6815 AD
    • Not yet recruiting
    • Rijnstate
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Universitair Medisch Centrum Groningen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has untreated Acute Myeloid Leukemia (AML)
• Have a documented IDH1 R132 gene-mutated disease
• Have at least one of the following making yourself ineligible for intensive chemotherapy (IC): 75 years or older, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2, or any comorbidity that the investigator judges to be incompatible with IC including but not limited to severe cardiac or pulmonary disorder, creatinine clearance less than 45 mL/minute, or bilirubin greater than 1.5 times the upper limit of normal
• Has adequate hepatic (liver) and renal (kidney) function
• Female participants of reproductive potential must have a negative blood pregnancy test and must use effective contraception during treatment and for at least 6 months following treatment
• Fertile male participants with female partners of reproductive potential must use effective contraception during treatment and for at least 3 months following treatment

Exclusion Criteria:

• Has received any prior treatment for AML, with the exception of hydroxyurea or leukapheresis for white blood cell count control
• Has received prior treatment with an IDH1 inhibitor
• Is a woman who is pregnant or breastfeeding
• Has an active, uncontrolled, systemic fungal, bacterial, or viral infection (including human immunodeficiency virus [HIV], active hepatitis B (HBV), or hepatitis C virus [HCV]) without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
• Has had significant active cardiac disease within 6 months prior to the start of study treatment, including Class III or IV congestive heart failure, myocardial infarction (heart attack), unstable angina (chest pain), and/or stroke
• Has dysphagia (difficulty swallowing), short-gut syndrome, gastroparesis (stomach paralysis), or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs
• Has uncontrolled hypertension (high blood pressure)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label Ivosidenib in combination with Azacitidine; All participants will receive both Ivosidenib and Azacitidine for a maximum of 28 cycles. Each cycle will be 4 weeks or 28 days long. Ivosidenib will be taken continuously throughout each cycle and Azacitidine will be taken only for 7 days at the beginning of each cycle.	Drug: Ivosidenib 500mg Oral Tablet; Provided as tablets, taken orally as two 250mg tablets once daily.; Drug: Azacitidine; Administered subcutaneously (SC) or intravenously (IV) at a dose of 75mg/m2/day for 7 days, either consecutively on Days 1-7 or discontinuously for Days 1-5 and 8-9 of each cycle. The 7 days of administration will occur at the beginning of every 4 week-long cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events (AEs)	Adverse events (AEs) will be graded according to the CTCAE v5.0	up to week 116
Number of Serious Adverse Events (SAEs)	Adverse events (AEs) will be graded according to the CTCAE v5.0	up to week 116
Differentiation Syndrome of Grade 2 or higher		up to week 116
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation		up to week 112
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption		up to week 112
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine dose reduction		up to week 112
Number of Adverse Events (AEs) leading to death		up to week 116
Number of clinical laboratory anomalies assessed as Adverse Events (AEs)		up to week 116
Number of patients requiring transfusion (platelet and RBC) and the average number of units transfused		up to week 116
Rate of infections	Infection rates will be summarized by classification and will include a count and proportion.	up to week 116
QT Prolongation event assessed as Grade 3 or higher		up to week 116

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)		up to week 116
Proportion of patients who achieve a complete remission (CR)		up to week 116
Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh)		up to week 116
Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi)		up to week 116
Duration of response (DOR)		up to week 116
Time to response (TTR)		up to week 116
Overall survival (OS)		until study closure
Quality of life (QoL), as measured by Hematologic Malignancy-Patient-Reported Outcome (HM-PRO)	For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score	up to week 116
Quality of life (QoL), as measured by Family Reported Outcome Measure (FROM-16), for caregivers and/or family	For patients with a baseline assessment and at least 1 post-baseline assessment that generates a score	up to week 116
Health economic measures, as assessed by the 5-level EuroQol 5-Dimensions (EQ-5D-5L)	For patients with a baseline assessment and at least 1 post-baseline assessment that generate a score	up to week 116
Average proportion of days at home	Defined by subtracting the number of care days (days hospitalized or seen in an ED / oncology clinic / infusion center) from the total days of follow-up, divided by total days of follow-up	up to week 116

Collaborators and Investigators

• Sponsor: Servier Affaires Médicales

Publications and helpful links

General Publications

• Vyas P, Salek S, Vives S, Recher C, Dohner H, Venditti A, Derrien H, Chatin S, De La Bigne AM, Pelouchova J, Hills R, Nier S. ALIDHE phase 3b study design: ivosidenib + azacitidine in adults with newly diagnosed IDH1 mutant acute myeloid leukemia. Future Oncol. 2025 Dec;21(29):3721-3729. doi: 10.1080/14796694.2025.2567838. Epub 2025 Nov 15.

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): October 15, 2027

Study Registration Dates

• First Submitted: June 8, 2023
• First Submitted That Met QC Criteria: June 8, 2023
• First Posted (Actual): June 18, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: IDH1 Mutation AML
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Dosage Forms; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Tablets; ivosidenib
• Other Study ID Numbers: DIM-95031-006; 2022-501709-11 (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
• product manufactured in and exported from the U.S.: Yes