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

NCT07726576 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: CHUBX 2024/37
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 3

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.

Conditions

Leukemia, Myeloid, Acute

Keywords

Acute myeloid leukemia; FLT3 mutation; midostaurin; venetoclax

Outcome Measures

Primary Outcomes (2)

• 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)

  Measured by multiparameter flow cytometry (MFC) according to European Leukemia Net (ELN) 2022

  From day 1 of induction chemotherapy up to 8 weeks

Secondary Outcomes (32)

• Phase 1:Number of participants with Dose Limiting Toxicities (DLTs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to treatment discontinuation

  From day 1 of induction chemotherapy up to 8 weeks, then from day 1 of each of 3 consolidation chemotherapy up to 8 weeks and from day 1 of first maintenance cycle up to 12 months

• Phase 1-2: Area under the concentration-time curve over a 12-hour dosing interval (- AUC 0-12h)

  From day 1 of induction chemotherapy up to 8 weeks, then from day 1 of each of 3 consolidation chemotherapy up to 8 weeks and from day 1 of first maintenance cycle up to 12 months

• Phase 1-2: Peak concentration (Cmax)

  From day 1 of induction chemotherapy up to 8 weeks, then from day 1 of each of 3 consolidation chemotherapy up to 8 weeks and from day 1 of first maintenance cycle up to 12 months

• Phase 1-2: Time to reach peak concentration (Tmax)

  From day 1 of induction chemotherapy up to 8 weeks, then from day 1 of each of 3 consolidation chemotherapy up to 8 weeks and from day 1 of first maintenance cycle up to 12 months

• Phase 1-2: Through concentration (Cmin)

  From day 1 of induction chemotherapy up to 8 weeks, then from day 1 of each of 3 consolidation chemotherapy up to 8 weeks and from day 1 of first maintenance cycle up to 12 months

Study Arms (1)

Standard treatment of FLT3 mutated AML

EXPERIMENTAL

Drug: Venetoclax in association with 3+7 and midostaurin

Interventions

Venetoclax in association with 3+7 and midostaurin DRUG

(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

Standard treatment of FLT3 mutated AML

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (3)

CH de la Côte Basque

Bayonne, 64100, France

Location

CHU de Bordeaux - Hôpital haut-Lévêque

Pessac, 33600, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Association; midostaurin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Psychotherapeutic Processes; Psychotherapy; Behavioral Disciplines and Activities

Central Study Contacts

Pierre-Yves DUMAS, PU-PH

CONTACT

+33 5 57 65 65 11; pierre-yves.dumas@chubordeaux.fr

Sarah BERTOLI

CONTACT

+33 5 31 15 62 69; bertoli.sarah@iuct-oncopole.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: July 24, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2031
• Last Updated: July 24, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)