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

AML, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06377579
• Other study ID #: FILObsLAM_IVOOBS
• Status: Not yet recruiting
• Start date: May 15, 2024
• Est. completion date: March 15, 2025

Study information

• Verified date: May 2024
• Source: French Innovative Leukemia Organisation
• Contact: Ariane MINEUR
• Phone: +33 (0)5 57 62 31 08
• Email: ariane.mineur[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 250
• Est. completion date: March 15, 2025
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• AML, Adult
• Leukemia, Myeloid, Acute

Locations

Country	Name	City	State
France	Amiens CHU	Amiens
France	Angers CHU	Angers
France	Bayonne CH	Bayonne
France	Besançon CHU	Besançon
France	CHU Estaing	Clermont-Ferrand
France	Créteil CHU HENRI MONDOR	Créteil
France	Grenoble CHU	Grenoble
France	Le Mans CH	Le Mans
France	Lyon sud CHU	Lyon
France	Marseille IPC	Marseille
France	Meaux CH de l'Est francilien	Meaux
France	Montpellier - Chu Saint Eloi	Montpellier
France	Nantes CHU	Nantes
France	Nice CHU	Nice
France	Orléans CHU	Orléans
France	Paris Saint Louis	Paris
France	Bordeaux CHU	Pessac
France	ICANS - Institut de cancérologie de strasbourg europe	Strasbourg
France	Toulouse - IUCT Oncopole - Service d'Hématologie	Toulouse

Sponsors (2)

Lead Sponsor	Collaborator
French Innovative Leukemia Organisation	Acute Leukemia French Association

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	characterize the composite response rate (CRc) at any time during follow-up, for the both cohort : 1st line and Relapsed/Refractory (R/R)	CRc is defined as the sum of Complete remission (CR) + Complete remission with partial hematological recovery (CRh) + Complete remission with incomplete count recovery (CRi) + MLFS, according to ELN 2022 criteria	6 months
Secondary	characterize the Event Free Survival (EFS) in both cohorts : 1st line and Relapsed/Refractory (R/R)	defined as the time from initiation of Ivosidenib (IVO) to the date of treatment failure, hematologic relapse from Complete remission (CR)/Complete remission with partial hematological recovery (CRh)/ Complete remission with incomplete count recovery (CRi)/ Morphologic leukemia-free state (MLFS) or death from any cause, whichever occurs first; Treatment failure is defined as not achieving either CR, CRh,CRi or MLFS by day 180 from Ivo start	6 months
Secondary	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)	description of grade 3/4 SAE and death according to CTCAE v5	6 months
Secondary	describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)	daily dose of Ivosidenib, description of Ivosidenib dose modification	6 months
Secondary	describe the management of treatment by Ivosidenib in both cohorts : 1st line and Relapsed/Refractory (R/R)	duration of treatment by Ivosidenib	6 months