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

Status: Recruiting
Location: See all (21) locations...
Study Type: Observational
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

Locations
Other Locations
France
Amiens CHU
NOT_YET_RECRUITING
Amiens
Angers CHU
NOT_YET_RECRUITING
Angers
Bayonne CH
NOT_YET_RECRUITING
Bayonne
Besançon CHU
NOT_YET_RECRUITING
Besançon
CHU Estaing
RECRUITING
Clermont-ferrand
Créteil CHU HENRI MONDOR
RECRUITING
Créteil
DUNKERQUE-Hôpital Alexandra Lepève
RECRUITING
Dunkirk
Grenoble CHU
NOT_YET_RECRUITING
Grenoble
Le Mans CH
NOT_YET_RECRUITING
Le Mans
Lyon sud CHU
NOT_YET_RECRUITING
Lyon
Marseille IPC
NOT_YET_RECRUITING
Marseille
Meaux CH de l'Est francilien
RECRUITING
Meaux
Montpellier - Chu Saint Eloi
NOT_YET_RECRUITING
Montpellier
Mulhouse Chu
RECRUITING
Mulhouse
Nantes CHU
RECRUITING
Nantes
Nice CHU
NOT_YET_RECRUITING
Nice
Orléans CHU
NOT_YET_RECRUITING
Orléans
Paris Saint Louis
NOT_YET_RECRUITING
Paris
Bordeaux CHU
NOT_YET_RECRUITING
Pessac
ICANS - Institut de cancérologie de strasbourg europe
NOT_YET_RECRUITING
Strasbourg
Toulouse - IUCT Oncopole - Service d'Hématologie
NOT_YET_RECRUITING
Toulouse
Contact Information
Primary
Ariane MINEUR
ariane.mineur@chu-bordeaux.fr
+33 (0)5 57 62 31 08
Time Frame
Start Date: 2024-07-31
Estimated Completion Date: 2025-12-01
Participants
Target number of participants: 250
Treatments
AML in 1st line at inclusion
AML in R/R at inclusion
Related Therapeutic Areas
Sponsors
Collaborators: Acute Leukemia French Association
Leads: French Innovative Leukemia Organisation

This content was sourced from clinicaltrials.gov

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