Clinical trial NCT06377579: OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
Official title: OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: AML, Adult
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
Collaborators: name: Acute Leukemia French Association
First posted: 2024-04-22
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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

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.


Eligibility criteria: 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

Primary outcomes:
measure: characterize the Overall survival (OS) in the both cohort : 1st line and Relapsed/Refractory (R/R)
timeFrame: 6 months
Secondary outcomes:
measure: characterize the composite response rate (CRc) at any time during follow-up, for the both cohort : 1st line and Relapsed/Refractory (R/R)
timeFrame: 6 months
measure: characterize the Event Free Survival (EFS) in both cohorts : 1st line and Relapsed/Refractory (R/R)
timeFrame: 6 months
measure: 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)
timeFrame: 6 months
measure: describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)
timeFrame: 6 months
measure: describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)
timeFrame: 6 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Amiens CHU
city: Angers
country: France
facility: Angers CHU
city: Bayonne
country: France
facility: Bayonne CH
city: Besançon
country: France
facility: Besançon CHU
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Créteil
country: France
facility: Créteil CHU HENRI MONDOR
city: Dunkerque
country: France
facility: DUNKERQUE-Hôpital Alexandra Lepève
city: Grenoble
country: France
facility: Grenoble CHU
city: Le Mans
country: France
facility: Le Mans CH
city: Lyon
country: France
facility: Lyon sud CHU
city: Marseille
country: France
facility: Marseille IPC
city: Meaux
country: France
facility: Meaux CH de l'Est francilien
city: Montpellier
country: France
facility: Montpellier - Chu Saint Eloi
city: Mulhouse
country: France
facility: Mulhouse Chu
city: Nantes
country: France
facility: Nantes CHU
city: Nice
country: France
facility: Nice CHU
city: Orléans
country: France
facility: Orléans CHU
city: Paris
country: France
facility: Paris Saint Louis
city: Pessac
country: France
facility: Bordeaux CHU
city: Strasbourg
country: France
facility: ICANS - Institut de cancérologie de strasbourg europe
city: Toulouse
country: France
facility: Toulouse - IUCT Oncopole - Service d'Hématologie
Study officials:
affiliation: French Innovative Leukemia Organisation
name: Pierre PETERLIN, Dr
role: PRINCIPAL_INVESTIGATOR
References: