protocolSection identificationModule nctId: NCT06377579, orgStudyIdInfo id: FILObsLAM_IVOOBS, briefTitle: OBServatory of Compassionate Use of IVOsidenib in France for Patients With Acute Myeloid Leukemia, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-05-15, primaryCompletionDateStruct date: 2024-12-15, completionDateStruct date: 2025-03-15, studyFirstPostDateStruct date: 2024-04-22, lastUpdatePostDateStruct date: 2024-04-22, sponsorCollaboratorsModule leadSponsor name: French Innovative Leukemia Organisation, class: OTHER, collaborators name: Acute Leukemia French Association, descriptionModule briefSummary: 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 diagnosisIvosidenib (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 (DiNardo et al. 2018) and in front line settings (Montesinos et al. 2022). 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, we 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. Our 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., conditionsModule conditions: AML, Adult, designModule studyType: OBSERVATIONAL, designInfo observationalModel: COHORT, timePerspective: CROSS_SECTIONAL, enrollmentInfo count: 250, type: ESTIMATED, armsInterventionsModule, outcomesModule primaryOutcomes measure: characterize the Overall survival (OS) in the both cohort : 1st line and Relapsed/Refractory (R/R), secondaryOutcomes measure: characterize the composite response rate (CRc) at any time during follow-up, for the both cohort : 1st line and Relapsed/Refractory (R/R), secondaryOutcomes measure: characterize the Event Free Survival (EFS) in both cohorts : 1st line and Relapsed/Refractory (R/R), secondaryOutcomes 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), secondaryOutcomes measure: describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R), eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Amiens CHU, city: Amiens, country: France, geoPoint lat: 49.9, lon: 2.3, locations facility: Angers CHU, city: Angers, country: France, geoPoint lat: 47.46667, lon: -0.55, locations facility: Bayonne CH, city: Bayonne, country: France, geoPoint lat: 43.48333, lon: -1.48333, locations facility: Besançon CHU, city: Besançon, country: France, geoPoint lat: 47.24878, lon: 6.01815, locations facility: CHU Estaing, city: Clermont-Ferrand, country: France, geoPoint lat: 45.77966, lon: 3.08628, locations facility: Créteil CHU HENRI MONDOR, city: Créteil, country: France, geoPoint lat: 48.78333, lon: 2.46667, locations facility: Grenoble CHU, city: Grenoble, country: France, geoPoint lat: 45.16667, lon: 5.71667, locations facility: Le Mans CH, city: Le Mans, country: France, geoPoint lat: 48.0, lon: 0.2, locations facility: Lyon sud CHU, city: Lyon, country: France, geoPoint lat: 45.74848, lon: 4.84669, locations facility: Marseille IPC, city: Marseille, country: France, geoPoint lat: 43.29551, lon: 5.38958, locations facility: Meaux CH de l'Est francilien, city: Meaux, country: France, geoPoint lat: 48.96014, lon: 2.87885, locations facility: Montpellier - Chu Saint Eloi, city: Montpellier, country: France, geoPoint lat: 43.61092, lon: 3.87723, locations facility: Nantes CHU, city: Nantes, country: France, geoPoint lat: 47.21725, lon: -1.55336, locations facility: Nice CHU, city: Nice, country: France, geoPoint lat: 43.70313, lon: 7.26608, locations facility: Orléans CHU, city: Orléans, zip: 45000, country: France, geoPoint lat: 47.90289, lon: 1.90389, locations facility: Paris Saint Louis, city: Paris, country: France, geoPoint lat: 48.85341, lon: 2.3488, locations facility: Bordeaux CHU, city: Pessac, country: France, geoPoint lat: 44.81011, lon: -0.64129, locations facility: ICANS - Institut de cancérologie de strasbourg europe, city: Strasbourg, country: France, geoPoint lat: 48.58392, lon: 7.74553, locations facility: Toulouse - IUCT Oncopole - Service d'Hématologie, city: Toulouse, country: France, geoPoint lat: 43.60426, lon: 1.44367, hasResults: False