The standard treatment for patients with acute myeloid leukemia (AML) with an abnormality in the IDH1 gene, who are not eligible for intensive chemotherapy, is a combination of ivosidenib and azacitidine. In this study it is investigated whether adding venetoclax to the standard treatment can improve the outcome of the treatment of this specific form of AML. The safety is investigated and how well it works. In order to properly assess the value of venetoclax, the effect of venetoclax is compared with the effect of a placebo. A placebo is a product without an active ingredient, a 'fake medicinal product'.
Patient with newly diagnosed IDH1-mutated AML, or IDH1-mutated MDS/AML according to the 2022 International Consensus Classification (Appendix A). Patients with AML with both IDH1 and IDH2 mutation are eligible as well. Of note: in case both NPM1 and IDH1 are mutated and both EVOLVE-1 (HO173/AMLSG 3423/ACT-HOV-AML-001) and EVOLVE-2 (HO177/AMLSG 35-24/ACT-HOV-AML-002are open for inclusion at your site, then patients can only be included in the EVOLVE-1 trial (HO173)
Central confirmation of IDH1 mutation in one of the dedicated central genetic laboratories.
Age ≥ 18 years, no upper age limit.
older than or equal to 75 years of age ineligible for intensive chemotherapy per physician's discretion (with an ECOG performance status 0-2; Appendix C).
Subject has previously been treated for AML; a treatment period with hydroxyurea to control WBC counts is allowed; prior treatment with a hypomethylating agent for MDS-EB is not allowed; prior treatment with erythropoiesis-stimulating agents or luspatercept for MDS is allowed.
Acute promyelocytic leukemia (APL) with t(15;17)(q24.1;q21.2); PML-RARA; or one of the other pathognomonic variant chromosomal translocations / fusion genes.
AML with BCR-ABL1; or myeloid blast crisis of CML
Severe cardiac arrhythmias
Stichting Hemato-Oncologie voor Volwassenen Nederland
Lead sponsor
German-Austrian Acute Myeloid Leukemia Study Group
Collaborator
United Kingdom AML Research Network
Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto
Collaborator
Swiss Group for Clinical Cancer Research (SAKK)
Collaborator
Danish Acute Leukemia Group
Collaborator
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Collaborator
Nordic AML Group
Collaborator