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.

NCT05907057 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: DIM-95031-0062022-501709-11
• Study Type: interventional
• Target: 245
• Locations: 4 countries
• Sites: 15

Brief Summary

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).

Conditions

Acute Myeloid Leukemia (AML)

Keywords

IDH1 Mutation AML

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (11)

• 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

Study Arms (1)

Open-Label Ivosidenib in combination with Azacitidine

EXPERIMENTAL

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; Drug: Azacitidine

Interventions

Ivosidenib 500mg Oral Tablet DRUG

Provided as tablets, taken orally as two 250mg tablets once daily.

Open-Label Ivosidenib in combination with Azacitidine

Azacitidine DRUG

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.

Open-Label Ivosidenib in combination with Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Servier Affaires Médicales: lead

Study Sites (15)

AKH - Medizinische Universität Wien

Vienna, 1090, Austria

COMPLETED

Klinikum Wels-Grieskirchen GmbH

Wels, 4600, Austria

COMPLETED

Institut Paoli Calmettes

Marseille, Bouches-du-Rhône, 13273, France

RECRUITING

CHU CAEN - Hôpital de la Côte de Nacre

Caen, Calvados, 14033, France

RECRUITING

CHU de Toulouse pt

Toulouse, Haute Garonne, 31059, France

RECRUITING

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, 35033, France

NOT YET RECRUITING

CHU Angers - Hôpital Hôtel Dieu

Angers, Liore, 49100, France

NOT YET RECRUITING

IRCCS Istituto Scientifico Romagnolo Per Lo Studio Dei Tumori "Dino Amadori" - IRST

Meldola, Forli-Cesena, 47014, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili)

Brescia, 25123, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

RECRUITING

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, 06135, Italy

RECRUITING

Meander Medisch Centrum

Amersfoort, 3818 AZ, Netherlands

RECRUITING

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

RECRUITING

Rijnstate

Arnhem, 6815 AD, Netherlands

NOT YET RECRUITING

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 41241779 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ivosidenib; Tablets; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Servier Affaires Médicales

CONTACT

+33 1 55 72 60 00; scientificinformation@servier.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2023
• First Posted: June 18, 2023
• Study Start: June 14, 2023
• Primary Completion (Estimated): October 15, 2027
• Study Completion (Estimated): October 15, 2027
• Last Updated: May 8, 2026

Record last verified: 2026-05

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.

Locations

AU (2); NL (4); FR (5); IT (4)