Informations générales (source: ClinicalTrials.gov)
OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
Observational [Patient Registry]
French Innovative Leukemia Organisation (Voir sur ClinicalTrials)
juillet 2024
décembre 2025
05 avril 2025
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.
Etablissements
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Amiens CHU - Amiens - France | Delphine Lebon, Dr | Contact (sur clinicalTrials) | |||
| Angers CHU - Angers - France | corentin Orvain, Dr | Contact (sur clinicalTrials) | |||
| Bayonne CH - Bayonne - France | Anne Banos, Dr | Contact (sur clinicalTrials) | |||
| Besançon CHU - Besançon - France | Yohann Desbrosses, Dr | Contact (sur clinicalTrials) | |||
| Bordeaux CHU - Pessac - France | Pierre-Yves Dumas, Prof | Contact (sur clinicalTrials) | |||
| CHU Estaing - Clermont-Ferrand - France | Gaspar Aspas Requena, MD | Contact (sur clinicalTrials) | |||
| Créteil CHU HENRI MONDOR - Créteil - France | Cécile Pautas, Dr | Contact (sur clinicalTrials) | |||
| DUNKERQUE-Hôpital Alexandra Lepève - 59385 - Dunkerque - France | Adrien DANIEL, Dr | Contact (sur clinicalTrials) | |||
| Grenoble CHU - Grenoble - France | Martin Carré, Dr | Contact (sur clinicalTrials) | |||
| ICANS - Institut de cancérologie de strasbourg europe - Strasbourg - France | Celestine SIMAND, Dr | Contact (sur clinicalTrials) | |||
| Le Mans CH - Le Mans - France | Kamel Laribi, Dr | Contact (sur clinicalTrials) | |||
| Lyon sud CHU - Lyon - France | Mael Heiblig, Pr | Contact (sur clinicalTrials) | |||
| Marseille IPC - Marseille - France | Sylvain GARCIAZ, Dr | Contact (sur clinicalTrials) | |||
| Meaux CH de l'Est francilien - Meaux - France | Jamilé Frayfer, Dr | Contact (sur clinicalTrials) | |||
| Montpellier - Chu Saint Eloi - Montpellier - France | Ludovic Gabellier, Dr | Contact (sur clinicalTrials) | |||
| Mulhouse Chu - 68100 - Mulhouse - France | Mario OJEDA-URIBE, Dr | Contact (sur clinicalTrials) | |||
| Nantes CHU - Nantes - France | Pierre Peterlin, Dr | Contact (sur clinicalTrials) | |||
| Nice CHU - Nice - France | Thomas Cluzeau, Prof | Contact (sur clinicalTrials) | |||
| Orléans CHU - 45000 - Orléans - France | Magda ALEXIS, Dr | Contact (sur clinicalTrials) | |||
| Paris Saint Louis - Paris - France | Emmanuel Raffoux, Prof | Contact (sur clinicalTrials) | |||
| Toulouse - IUCT Oncopole - Service d'Hématologie - Toulouse - France | Sarah BERTOLI, Dr | Contact (sur clinicalTrials) | |||
Critères
Tous
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.
- 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.
- Patients who expressed their opposition to entered in the study
- Patients who received IVO through a trial