OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia

November 25, 2025 updated by: French Innovative Leukemia Organisation

Mutations in IDH genes are found in numerous cancers and more specifically in acute myeloid leukemia (AML). These mutations target specific amino acids, at positions 140 or 172 of IDH2, and 132 of IDH1. Mutant IDH proteins acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) into D-2 hydroxyglutarate (D-2HG), an oncometabolite which massively accumulates in IDH-mutated cells. At high levels, D-2HG behaves as a competitive inhibitor of αKG and affects the activity of Fe(II)/αKG-dependent dioxygenases. This enzymatic family is involved in a broad spectrum of pathways such as demethylation of histone (JHDM histone demethylases) or DNA (methylcytosine hydroxylases of the TET family). As a result, IDH-mutated cells show altered survival, motility, invasiveness and cell differentiation. In AML, IDH1 mutations might be present in 10-15% at diagnosis

Ivosidenib (IVO) a first-in-class, oral, irreversible inhibitor of mutant IDH1 has shown clinical activity as a single agent in studies involving patients with IDH1 mutated relapsed or refractory (R/R) AML and in front line settings. In phase II clinical trials, IVO yielded 30-35% of complete response rates both in frontline and R/R settings, with long lasting responses. Based on these results, the FDA (Food and Drug Agency) gave its approval for newly-diagnosed AML IDH1mut patients who are ≥ 75 years old or who have comorbidities and in R/R. However, European Medicines Agency (EMA)'s did not approved IVO due to lack of evidences to support the application. Agios Netherlands B.V. (the company that previously own the drug before Servier Laboratories) withdrew its EMA application. Nevertheless, IVO has been available in France through a compassionate use program (CUP), since February 2020 for R/R patients and March 2022 for first line treatment.

In this multicentric retrospective study, sponsor aim to evaluate the efficacy and safety of Ivo in two cohorts of IDH1mut AML patients treated within the CUP. The first cohort will concern patients treated in first line setting and the second cohort those treated in R/R disease. Results might provide new insights regarding IVO in real life settings and support signs of efficacy. This could provide new data for the haematologist community and for another appliance to grant EMA approval of IVO in the setting of R/R IDH1mut AML.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

250

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 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

Sampling Method

Probability Sample

Study Population

Patients of 18 years old or more, with newly diagnosed or relapsed or refractory IDH1 mutated AML according to ELN 2022 and treated with IVO thanks to the CUP between the period 01/01/2017 to 01/08/2023, treated in French AML FILO or ALFA centers

Description

Inclusion Criteria:

  • Patient with IDH1 R132 mutated with newly diagnosed or Relapsed or Refractory (R/R) acute myeloid leukemia
  • Patient treated within French compassionate access program that have started the treatment between 01/01/2017 to 01/08/2023
  • patient treated by Ivosidenib received either as a monotherapy or in combination with other AML therapy (i.e. azacytidine, venetoclax)
  • Patient not included within IDH inhibitor clinical trial.

Exclusion Criteria:

  • Patients who expressed their opposition to entered in the study
  • Patients who received IVO through a trial

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

Cohorts and Interventions

Group / Cohort
AML in 1st line at inclusion
AML in R/R at inclusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
characterize the Overall survival (OS) in the both cohort : 1st line and Relapsed/Refractory (R/R)
Time Frame: 6 months

defined as the time from date of initiation of Ivosidebib to date of death due to any cause.

Patients still alive or lost to follow up will be censored at the time they were last known to be alive
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
characterize the composite response rate (CRc) at any time during follow-up, for the both cohort : 1st line and Relapsed/Refractory (R/R)
Time Frame: 6 months
CRc is defined as the sum of Complete remission (CR) + Complete remission with partial hematological recovery (CRh) + Complete remission with incomplete count recovery (CRi) + MLFS, according to ELN 2022 criteria
6 months
characterize the Event Free Survival (EFS) in both cohorts : 1st line and Relapsed/Refractory (R/R)
Time Frame: 6 months
defined as the time from initiation of Ivosidenib (IVO) to the date of treatment failure, hematologic relapse from Complete remission (CR)/Complete remission with partial hematological recovery (CRh)/ Complete remission with incomplete count recovery (CRi)/ Morphologic leukemia-free state (MLFS) or death from any cause, whichever occurs first; Treatment failure is defined as not achieving either CR, CRh,CRi or MLFS by day 180 from Ivo start
6 months
characterize the incidence and relatedness of serious adverse events (SAE), for patients treated by Ivosidenib, for both cohorts : 1st line and Relapsed/Refractory (R/R)
Time Frame: 6 months
description of grade 3/4 SAE and death according to CTCAE v5
6 months
describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)
Time Frame: 6 months
daily dose of Ivosidenib, description of Ivosidenib dose modification
6 months
describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)
Time Frame: 6 months
duration of treatment by Ivosidenib
6 months

Collaborators and Investigators

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

Sponsor

French Innovative Leukemia Organisation

Collaborators

Acute Leukemia French Association

Investigators

  • Principal Investigator: Pierre PETERLIN, Dr, French Innovative Leukemia Organisation

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 (Actual)

July 31, 2024

Primary Completion (Actual)

August 30, 2025

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

April 17, 2024

First Submitted That Met QC Criteria

April 17, 2024

First Posted (Actual)

April 22, 2024

Study Record Updates

Last Update Posted (Actual)

November 26, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FILObsLAM_IVOOBS

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

product manufactured in and exported from the U.S.

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.

Clinical Trials on AML, Adult

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Austria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe