Venetoclax in Association With 3+7 and Midostaurin in FLT3-mutated Acute Myeloid Leukemia | NCT07726576

NCT07726576

Overview

NCT ID: NCT07726576
Lead Sponsor: University Hospital, BordeauxOTHER
Official Title: Phase 1/2 Evaluating the Addition of Venetoclax to Standard 3+7 and Midostaurin Induction Treatment in Patients With FLT3-mutated Acute Myeloid Leukemia Eligible to Intensive Chemotherapy - MIDOVEN
Brief Summary: Acute myeloid leukemia (AML) with FLT3 mutation accounts for 30% of patients and is associated with a poor prognosis. Because of the FLT3 mutation, a tyrosine kinase inhibitor, midostaurin (MIDO), is added to the standard treatment with daunorubicin and cytarabine, from D8 to D21 of induction and of each consolidation cycle, followed by one year of maintenance. Venetoclax (VEN), a BCL2 inhibitor, has revolutionized the management of AML patients ineligible for intensive chemotherapy, in combination with azacitidine or cytarabine. The investigators hypothesize that a four-drug induction regimen (daunorubicin+cytarabine+MIDO+VEN) will increase complete remission (CR) rate without measurable residual disease (MRD) and improve event free survival (EFS), relapse free survival (RFS) and overall survival (OS) of this subgroup of patients with unmet medical need.

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: No
Eligibility Criteria: Main inclusion criteria:

Age ≥18 years and ≤70 years

Newly diagnosed AML according to World Health Organization (WHO) 2022 classification

Documented FLT3 gene mutation (-TKD D835 or I836 or -ITD or both) FLT3-ITD is assessed by DNA fragment analysis. Positivity is defined as an ITD/wt ratio of ≥ 0.05 (5%).

FLT3-TKD D835 or I836 is assessed by NGS. Positivity is defined as a VAF > 5%.

Patient must be eligible for intensive chemotherapy.

Main exclusion criteria:

Prior treatment for AML or myelodysplastic (MDS) phase.

Prior exposure to VEN or other BCL2 inhibitors

AML secondary to prior hematological disorders, including myelodysplastic syndrome, myeloproliferative disorders and/or therapy-related AML.

Acute promyelocytic leukemia, CBF-AML, Phi+ AML

Significant active cardiac disease within 6 months prior to the start of study treatment or QTc interval using Fridericia's formula (QTcF) ≥ 450 msec.

Cardiac ejection fraction <45%

Central Contacts: Pierre-Yves DUMAS, PU-PHContact
pierre-yves.dumas@chubordeaux.fr+33 5 57 65 65 11