Study Evaluating the Efficacy and Safety of the Addition of Ivosidenib to Oral Azacitidine (Onureg®) in Patients Over 55 With Acute Myeloid Leukemia (AML) and IDH1 Mutation, in Complete Remission After Intensive Chemotherapy. (MIVONU)

March 10, 2026 updated by: French Innovative Leukemia Organisation

A Single Arm Phase II Study Investigating the Efficacy and Safety of the Addition of Ivosidenib to Oral Azacitidine (Onureg®) in Patients Over 55 With Acute Myeloid Leukemia (AML) and IDH1 Mutation, in Complete Remission After Intensive Chemotherapy. A Study of the French AML Intergroup.

After remission post-induction and consolidation, maintenance therapy by an ivosidenib and oral azacitidine combination is susceptible to improve the prevention of AML relapse, which remains a major issue in the study population. We assume that the combination of ivosidenib with oral azacitidine will not be less well tolerated than in combination with the subcutaneous form, therapeutic regimen authorized until progression or toxicity. Ivosidenib and Onureg®, being already authorized treatments, it has been decided to use the classic administration schedules and dosages in combination.

The primary objective of the study is to evaluate relapse free survival (RFS) at 24 months in patients receiving oral azacitidine with ivosidenib.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

According to data from the Institut de Veille Sanitaire, the frequency of Acute Myeloid Leukemia (AML) is about 3 cases per 100,000 inhabitants, a frequency which increases with age to reach 20 / 100,000 at 70 years. AML is characterized by recurrent molecular and cytogenetic abnormalities. Among mutations arising with age, those of IDH1 (isocitrate dehydrogenase 1) and IDH2 ((isocitrate dehydrogenase 2) are considered as early molecular events driving AML transformation, characterized by a DNA hypermethylation signature. Somatic mutations in the gene encoding IDH1 occur in 6 to 16% of patients with AML.

In intensively treated (ICT) patients, IDH1 mutations are associated with a poorer outcome in patients treated with ICy34, even in case of favorable-ELN risk. Hematopoietic stem cell transplantation (HSCT) for IDH1mut patients in CR1 after ICT drastically improves OS (HR, 0.48; P = .048). However, in real life settings, and more specifically in elderly patients, only 40% of patients with HSCT indication are effectively transplanted.

For patients who are not candidates for HSCT, effective AML maintenance therapies are needed that can reduce the risk of relapse and prolong overall survival without causing undue adverse effects or compromising health-related quality of life. Indeed, relapse rates after IC without HSCT remain high with limited therapeutic options in this setting. There is a clear unmet medical need to improve the outcome of patients treated with IC who are not candidate for HSCT.

Oral azacitidine is approved as maintenance therapy in adult AML patients who achieve CR or CR without blood count recovery (CRi), following induction therapy and are not eligible for allo-HCT. Nevertheless, according to results of the pivotal QUAZAR-AML-001 placebo-controlled trial, estimated 5-year overall survival reached only 26% in the oral azacitidine arm versus 20% in the placebo arm.

Ivosidenib, a first-in-class, oral, potent, targeted small-molecule inhibitor of mutant IDH1, has shown clinical activity as a single agent in studies involving patients with hematologic and solid-tumors. In a phase 1 dose-escalation and dose-expansion study of ivosidenib monotherapy in IDH1-mutated relapsed or refractory AML, the rate of CR or CRi was 30,4%.

For newly diagnosed patients with IDH1 mutation, results from a randomized study (AGILE trial) indicate that the IDH1 inhibitor ivosidenib plus azacitidine improves event-free survival (EFS) (hazard ratio, 0.33; 95% CI, 0.16-0.69), clinical response (CR/CRh, 52.8 vs 17.6%), and median OS (29.3 vs 7.9 months) compared with azacitidine plus placebo.

After remission post-induction and consolidation, maintenance therapy by an ivosidenib and oral azacitidine combination is susceptible to improve the prevention of AML relapse, which remains a major issue in the study population. We assume that the combination of ivosidenib with oral azacitidine will not be less well tolerated than in combination with the subcutaneous form, therapeutic regimen authorized until progression or toxicity. Ivosidenib and Onureg®, being already authorized treatments, it has been decided to use the classic administration schedules and dosages in combination

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female ≥ 55 years of age at the time of signing informed consent
  2. Patients with confirmation of newly diagnosed AML by 2022 WHO criteria
  3. Presence of IDH1 R132 mutation at AML diagnosis
  4. Achievement CR or CRi following induction therapy by intensive chemotherapy (according to ELN 2022, appendix 2), within 17 weeks prior to enrollment.

  5. Received at least 2 consolidations :

    1. with intermediate dose of cytarabine (IDAC)
    2. or with standard dose cytarabine and idarubicin (5+1)
  6. Adequate BM function: ANC ≥1 × 109/L and platelet count ≥50 × 109/L at the time of inclusion
  7. Patients who are not candidate for Allo-HSCT

  8. Adequate baseline organ function defined by the following criteria:

    • Estimated Glomerular Filtration Rate (eGFR) ≥ 30 ml/min (using CKD-EPI).
    • aspartate aminotransferase (AST) ≤ 2.5 × ULN
    • alanine aminotransferase (ALT) ≤ 2.5× ULN
    • bilirubin ≤ 1.5 × ULN
  9. ECOG < 3 (appendix 1)
  10. Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule
  11. Patient suitable for oral administration of study drug.

  12. A female subject is eligible to participate if she is not pregnant and at least one of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP) as defined in post-menopausal (defined as at least 1 year without any menses) prior to Screening, or documented as surgically sterile (at least 1 month prior to Screening)
    2. WOCBP agrees to follow the contraceptive treatment starting at screening and continued throughout the study period, and for at least 180 days after the final study drug administration.
    3. WOCBP agrees to perform planned pregnancy tests in the study
  13. Female subject must agree not to breastfeed starting at screening and throughout the study period, and for one month after the final study drug administration.
  14. Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration.
  15. A male subject with a partner(s) of childbearing potential must agree to use contraception starting at screening and continue throughout the study period, for at least 90 days after the final study drug administration.
  16. A male subject must not donate sperm starting at screening nor throughout the study period and for 90 days after the final study drug administration
  17. Patient must be affiliated to the French social security (health insurance)
  18. Signed written informed consent for the study

Exclusion Criteria:

  1. Acute promyelocytic leukemia (FAB M3) with t(15;17) or its molecular equivalents (PML::RARA)
  2. AML associated with t(9;22) or molecular evidence of such a translocation
  3. Prior BM or hematopoietic stem cell transplantation
  4. CR/CRi following treatment with hypomethylating agents
  5. Proven central nervous system leukemia
  6. Candidate for Allo-HSCT at screening
  7. Diagnosis of malignant disease within the previous 12 months (excluding MDS or CMML, basal cell carcinoma of the skin without complications, "in- situ" carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure)

  8. Abnormal cardiac status with any of the following:

    • Unstable angina
    • Myocardial infarction within the last 6 months
    • Significant cardiac arrhythmia
    • New York Heart Association (NYHA) class 3 or 4 congestive heart failure
    • Congenital long QT syndrome, familial history of sudden death or polymorphic ventricular arrhythmias and QT/QTc interval > 500 msec regardless of the correction method.

    For subject with 450 ≤ QTc ≤ 500 ms, practitioners should thoroughly reassess the benefit/risk of initiating ivosidenib. In case QTc interval prolongation is between 480 msec and 500 msec, initiation of treatment with ivosidenib should remain exceptional and be accompanied by close monitoring. This issue will be discussed with coordinating investigator.

  9. Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment)
  10. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
  11. Severe medical or mental condition precluding the administration of protocol treatments
  12. Persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure (guardianship, curatorship, legal protection), persons under psychiatric care
  13. Other comorbidity that the physician judges to be incompatible with the study design
  14. Any condition causing an inability to swallow tablets or known hypersensitivity to the study medication
  15. Any condition that would impair absorption of the study medication (i.e. short gut, malabsorption syndrome)
  16. Subject requiring treatment with concomitant drugs that are strong inducers/inhibitors of cytochrome P450 (CYP)3A /PGP or dabigatran (PGP substrate) (see appendix 6) or QT-prolongating agent other than 5-HT3 antagonists (see appendix 8) or other forbidden medications listed in section 10.7
  17. Subject with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
  18. Subject with positive HIV test treated or planned to be treated with drugs with potential drug-drug interactions. HIV testing will be performed at screening, if required per local guidelines or institutional standards.
  19. Subject known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status with undetectable PCR viral load on antivirals (non-exclusionary medications) are not excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ivosidenib + Oral azacitidine
cf intervention
Drug: Ivosidenib + oral azacitidine

Subjects will be administered treatment over 28-day cycles until progression or another reason (unacceptable toxicity, patient choice to discontinue study treatment, sponsor decision, HSCT at any time, patients who require the use of any of the excluded therapies).

The treatment is the association of ivosidenib with oral azacitidine.

  • The investigational medicinal product is ivosidenib. Two tablets (500 mg) will be administered as a single dose, once daily, during 28 days-cycles until discontinuation.
  • The auxiliary treatment is oral azacitidine. Oral AZA 300 mg will be given once-daily for 14 days of repeated 28-day treatment cycles. For all patients, oral AZA will be interrupted systematically after day 14 of each 28-days cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RFS 24 months
Time Frame: 24 months
relapse-free-survival (RFS) at 24 months in patients receiving oral azacitidine with ivosidenib
24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RFS 12 months
Time Frame: 12 months
RFS at 12 months, with the same definition for RFS as for the primary endpoint
12 months
Overall survival
Time Frame: 24 months
Overall survival defined as the time between inclusion assignment and death from any cause, at 12 and 24 months
24 months
EFS MRD neg
Time Frame: 24 months
EFS MRD-, defined in patients who were MRD negative at baseline to MRD relapse (by FCM or RT-qPC for NPM1) or death from any cause, whichever occurred first
24 months
TEAEs
Time Frame: 24 months
Number of participants with Treatment Emergent Adverse Events (TEAEs), according the CTCAE v5.0 classification
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

French Innovative Leukemia Organisation

Collaborators

Servier Affaires Médicales

Investigators

  • Principal Investigator: Arnaud PIGNEUX, University Hospital, Bordeaux
  • Principal Investigator: Stephane DE BOTTON, Gustave Roussy, Cancer Campus, Grand Paris
  • Principal Investigator: Maël HEIBLIG, Centre hospitalier Lyon Sud
  • Principal Investigator: Yohan DESBROSSES, CHRU Jean Minjoz Besançon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

September 1, 2030

Study Completion (Estimated)

September 1, 2030

Study Registration Dates

First Submitted

February 18, 2026

First Submitted That Met QC Criteria

March 10, 2026

First Posted (Actual)

March 11, 2026

Study Record Updates

Last Update Posted (Actual)

March 11, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FILO-AML-01-MIVONU

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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