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

NCT07726576 · tracked via the Priya Life Science France tracker

Sponsor

University Hospital, Bordeaux

Phase

Phase 1/2

Started

2026-09

Last updated

2026-07-24

Condition(s) studied

Leukemia, Myeloid, Acute

Investigational drug(s) / intervention(s)

Venetoclax in association with 3+7 and midostaurin

Venetoclax in association with 3+7 and midostaurin: (1) induction with daunorubicin 60 mg/m²/day for 3 days, cytarabine 200 mg/m²/day for 7 days and MIDO 50 mg x 2/day from D8 to D21, (2) consolidation with 3 courses of intermediate dose cytarabine 1-1.5 gr/m² x 2/day at D1, D2 and D3 and MIDO 50 mg x 2/day from D8 to D21 in 35-day cycles, and (3) a maintenance with MIDO 50 mg x 2/day from D1 to D28 in 28-day cycles for 12 cycles. VEN is a highly potent BCL-2 inhibitor, synergistic with cytarabine, anthracyclines, and tyrosine kinase inhibitors. In the current study we aim at harnessing this synergistic effect with standard chemotherapy (cytarabine, anthracyclines) and tyrosine kinase inhibitor (MIDO) during induction, consolidation and maintenance. Our strategy aims at determining the best schedule of combination during induction chemotherapy whereas we do not foresee specific safety issues during consolidation and maintenance strategy

Study 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

70 Years

Healthy volunteers

Main inclusion criteria: 1. Age ≥18 years and ≤70 years 2. Newly diagnosed AML according to World Health Organization (WHO) 2022 classification 3. 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%. 4. Patient must be eligible for intensive chemotherapy. Main exclusion criteria: 1. Prior treatment for AML or myelodysplastic (MDS) phase. 2. Prior exposure to VEN or other BCL2 inhibitors 3. AML secondary to prior hematological disorders, including myelodysplastic syndrome, myeloproliferative disorders and/or therapy-related AML. 4. Acute promyelocytic leukemia, CBF-AML, Phi+ AML 5. Significant active cardiac disease within 6 months prior to the start of study treatment or QTc interval using Fridericia's formula (QTcF) ≥ 450 msec. 6. Cardiac ejection fraction \<45%

Primary outcome measure(s)

Phase 1: Maximum tolerated schedule (MTS) of VEN in combination with 3+7+MIDO to define the recommended phase 2 schedule (RP2S). — From day 1 of induction chemotherapy up to 8 weeks
Phase 2: Proportion of participants with complete remission (CR)/CR with incomplete hematologic recovery (CRi) without measurable residual disease (MRD) — From day 1 of induction chemotherapy up to 8 weeks
Measured by multiparameter flow cytometry (MFC) according to European Leukemia Net (ELN) 2022

Trial sites (3)

Facility	City	Region
CH de la Côte Basque	Bayonne	France
CHU de Bordeaux - Hôpital haut-Lévêque	Pessac	France
CHU de Toulouse	Toulouse	France

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07726576 on ClinicalTrials.gov ↗ ← All trials in France