NCT06377579

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
250

participants targeted

Target at P75+ for all trials

Timeline
0mo left

Started Jul 2024

Geographic Reach
1 country

21 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress96%
Jul 2024Jun 2026

First Submitted

Initial submission to the registry

April 17, 2024

Completed
5 days until next milestone

First Posted

Study publicly available on registry

April 22, 2024

Completed
3 months until next milestone

Study Start

First participant enrolled

July 31, 2024

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2025

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2026

Expected
Last Updated

November 26, 2025

Status Verified

November 1, 2025

Enrollment Period

1.1 years

First QC Date

April 17, 2024

Last Update Submit

November 25, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • characterize the Overall survival (OS) in the both cohort : 1st line and Relapsed/Refractory (R/R)

    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 Outcomes (5)

  • characterize the composite response rate (CRc) at any time during follow-up, for the both cohort : 1st line and Relapsed/Refractory (R/R)

    6 months

  • characterize the Event Free Survival (EFS) in both cohorts : 1st line and Relapsed/Refractory (R/R)

    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)

    6 months

  • describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)

    6 months

  • describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)

    6 months

Study Arms (2)

AML in 1st line at inclusion

AML in R/R at inclusion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability 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

You may qualify if:

  • 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.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Amiens CHU

Amiens, France

NOT YET RECRUITING

Angers CHU

Angers, France

NOT YET RECRUITING

Bayonne CH

Bayonne, France

NOT YET RECRUITING

Besançon CHU

Besançon, France

NOT YET RECRUITING

CHU Estaing

Clermont-Ferrand, France

RECRUITING

Créteil CHU HENRI MONDOR

Créteil, France

RECRUITING

DUNKERQUE-Hôpital Alexandra Lepève

Dunkirk, 59385, France

RECRUITING

Grenoble CHU

Grenoble, France

NOT YET RECRUITING

Le Mans CH

Le Mans, France

NOT YET RECRUITING

Lyon sud CHU

Lyon, France

NOT YET RECRUITING

Marseille IPC

Marseille, France

NOT YET RECRUITING

Meaux CH de l'Est francilien

Meaux, France

RECRUITING

Montpellier - Chu Saint Eloi

Montpellier, France

NOT YET RECRUITING

Mulhouse Chu

Mulhouse, 68100, France

RECRUITING

Nantes CHU

Nantes, France

RECRUITING

Nice CHU

Nice, France

NOT YET RECRUITING

Orléans CHU

Orléans, 45000, France

NOT YET RECRUITING

Paris Saint Louis

Paris, France

NOT YET RECRUITING

Bordeaux CHU

Pessac, France

NOT YET RECRUITING

ICANS - Institut de cancérologie de strasbourg europe

Strasbourg, France

NOT YET RECRUITING

Toulouse - IUCT Oncopole - Service d'Hématologie

Toulouse, France

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Study Officials

  • Pierre PETERLIN, Dr

    French Innovative Leukemia Organisation

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
CROSS SECTIONAL
Target Duration
6 Months
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 17, 2024

First Posted

April 22, 2024

Study Start

July 31, 2024

Primary Completion

August 30, 2025

Study Completion (Estimated)

June 1, 2026

Last Updated

November 26, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will not share

Locations