Leukemia, Myeloid, AcutePhase 1/2MIDOVENNCT07726576
Venetoclax in Association With 3+7 and Midostaurin in FLT3-mutated Acute Myeloid Leukemia
A Phase 1/2 study testing Venetoclax in association with 3+7 and midostaurin in people with Leukemia, Myeloid, Acute, run by University Hospital, Bordeaux at 3 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- Venetoclax in association with 3+7 and midostaurin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 3 sitesFrance
- Study dates
- Sep 2026to Dec 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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%
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites
CH de la Côte Basque
Bayonne, 64100
Anne BANOS, Dr, +33 5 59 44 38 32, abanos@ch-cotebasque.fr
CHU de Bordeaux - Hôpital haut-Lévêque
Pessac, 33600
Pierre-Yves DUMAS, PU-PH, +33 5 57 65 65 11, pierre-yves.dumas@chu-bordeaux.fr
CHU de Toulouse
Toulouse, 31059
Sarah BERTOLI, Dr, +33 5 31 15 62 69, bertoli.sarah@iuct-oncopole.fr
About this study
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
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.
Read the detailed description
Screening of 226 clinical trials on ClinTrial.gov showed 26 studies evaluating intensive chemotherapy (daunorubicin+cytarabine) and VEN but none in combination with MIDO even though 30% of patients eligible for intensive chemotherapy do receive such a regimen. Intensive chemotherapy and MIDO showed a significant median overall survival improvement but a moderate increase of patients still alive at 3 years, around an additional 10% 1. Moreover, MIDO does not allow an increase in proportion of patients in first complete remission (CR1) or CR with incomplete hematologic recovery (CRi1) after the 1st induction course. Another study with a second-generation tyrosine kinase inhibitor, quizartinib (QuANTUM-First) showed that among patients with CR1/CRi1, 42% had a measurable residual disease (MRD) <10-4 in quizartinib arm versus 38% in placebo arm, despite, here again, a significant median overall survival improvement 2. These data show that tyrosine kinase inhibitors do not increase the rate of complete remission (CR) without MRD, explaining probably the moderate improvement of definitive cure rate. The investigators hypothesize that adding VEN to this standard treatment will increase complete remission rate without MRD and improve OS of patients with FLT3-mutated AML. Two clinical trials evaluated VEN in AML patients eligible to intensive chemotherapy and showed high levels of complete remission without MRD and a manageable toxicity profile, related to VEN start date and duration of exposure 3,4. In the current study, the investigators propose the following schedule to find the best treatment sequence while preventing the risk of myelosuppression, based on available data from the two clinical trials previously presented: In schedule A, VEN will be used from D8 to D14 to harness the synergy between FLT3 and BCL2 inhibition; in schedule B, VEN will be used from D4 to D10 to harness the synergy between chemotherapy and BCL2 inhibition then between FLT3 and BCL2 inhibition. If previous schedules A and B are safe, the investigators propose to prolong VEN exposure to 10 days allowing longer association between MIDO and VEN with a schedule C with VEN from D8 to D17 and finally a schedule D with VEN from D4 to D13. Follow-up will include up to 3 consolidation courses with intermediate dose cytarabine and VEN according to previous French phase 2 clinical trial COVENIDAC 5 and MIDO in this label from D8 to D21. Finally, patients will receive 12 cycles maintenance by MIDO with VEN D1-D14 in 28-day cycles. Patients will undergo allogeneic stem cell transplantation (HSCT) according to standard indications and procedures.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Venetoclax in association with 3+7 and midostaurin
- Keywords
- Acute myeloid leukemia, FLT3 mutation, midostaurin, venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venetoclax in association with 3+7 and midostaurinDrug
(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 group | Role | What they receive |
|---|---|---|
| Standard treatment of FLT3 mutated AML | Experimental | Not described Receives: Drug: Venetoclax in association with 3+7 and midostaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum tolerated schedule (MTS) of VEN in combination with 3+7+MIDO to define the recommended phase 2 schedule (RP2S).
Measured: 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
Measured: 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
Number of participants with Dose Limiting Toxicities (DLTs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to treatment discontinuation, defined according to the NCI CTCAE v5
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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: Steady-state accumulation ratios of AUC 0-12h
Measured: 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: Steady-state accumulation ratios of Cmax
Measured: 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 plasma concentration-time profile from time zero to time tau (AUCtau)
Measured: 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 extrapolated to infinity (AUCinf)
Measured: 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: Half time (T1/2)
Measured: 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: Oral clearance (CL/F)
Measured: 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: Volume or volume/kg (Vz/F)
Measured: 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 2: Number of participants experiencing at least one treatment-related adverse event, or at least one serious treatment-related adverse event
Number of participants experiencing at least one treatment-related adverse event, or at least one serious treatment-related adverse event, , defined according to the NCI CTCAE v5
Measured: 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 2: Number of participants experiencing at least one adverse event that led to discontinuation of treatment
Number of participants experiencing at least one adverse event that led to discontinuation of treatment, defined according to the NCI CTCAE v5
Measured: 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: Proportion of participants with complete remission (CR)/CR with incomplete hematologic recovery (CRi) without measurable residual disease (MRD)
Measured by MFC according to ELN2022 and with a sensitivity at 10-4 or limit of detection (LOD)
Measured: Day 1 of Consolidation 2, day 1 of consolidation 3 , day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, day 1 of maintenance cycle 7, day 1 of maintenance cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with complete remission (CR), CR with incomplete hematologic recovery (Cri), CR with partial hematological recovery (CRh), morphologic leukemia free state (MLFS), partial response (PR), no response, non-evaluable for response
Measured: From day 1 of induction chemotherapy up to 8 weeks
Proportion of participants with CR/CRi/CRh without MRD
Measured by MFC according to ELN2022 and with a sensitivity at 10-4 or LOD
Measured: Day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, day 1 of maintenance cycle 7, day 1 of maintenance cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi without MRD
Measured by RT-qPCR on NPM1 in co-mutated FLT3 and NPM1 subgroup
Measured: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi/CRh without MRD
Measured by RT-qPCR on NPM1 in co-mutated FLT3 and NPM1 subgroup
Measured: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi with MRD low-level (MRDLL)
Measured by RT-qPCR on NPM1 in co-mutated FLT3 and NPM1 subgroup
Measured: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi/CRh with MRDLL
Measured by RT-qPCR on NPM1 in co-mutated FLT3 and NPM1 subgroup
Measured: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi without MRD
Measured by NGS on FLT3 in FLT3-ITD subgroup
Measured: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi/CRh without MRD
Measured by NGS on FLT3 in FLT3-ITD subgroup
Measured: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Overall survival (OS)
Time from start of treatment to death due to any cause
Measured: From day 1 of inclusion until the date of end of study or to the date of death from any cause
Event-free survival (EFS) and EFS including MRD relapse (RT-qPCR on NPM1 and/or NGS FLT3-ITD and/or MFC) as event (EFSMRD)
From day 1 of inclusion to the date of treatment failure, hematologic relapse from CR/CRh/CRi or death from any cause, whichever occurs first (ELN 2022 criteria). MRD relapse is also considered as an event for EFSMRD
Measured: From date of day 1 of induction chemotherapy until the date of first documented progression, including molecular progression or date of death from any cause, whichever came first, assessed up to 24 months
Relapse-free survival (RFS), and RFS including MRD relapse (RT-qPCR on NPM1 and/or NGS FLT3-ITD and/or MFC) as event (RFSMRD)
Defined only for patients achieving CR, CRh, or CRi; measured from the date of achievement of remission until the date of hematologic relapse or death from any cause (ELN 2022 criteria). MRD relapse is also considered as an event for RFSMRD
Measured: From date of CR until the date of first documented progression, including molecular progression or date of death from any cause, whichever came first, assessed up to 24 months
Cumulative incidence of relapse (CIR), and CIR including MRD relapse (RT-qPCR on NPM1 and/or NGS FLT3-ITD and/or MFC) as event (CIRMRD)
Defined for all patients achieving CR, CRh, CRi; measured from the date of achievement of a remission until the date of hematologic relapse (ELN 2022 criteria). MRD relapse is also considered as an event for CIRMRD
Measured: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
Proportion of participants with HSCT performed in CR/CRi in eligible patients
Measured: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
Proportion of participants with HSCT performed CR/CRi/CRh in eligible patients
Measured: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
Proportion of participants with HSCT performed in CR/CRi/CRh/MLFS in eligible patients
Measured: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
To describe PK of VEN
During induction, plasma samples will be collected at the following time points for VEN treatment: Pre-dose, 1, 2, 4, and a last one between 6- and 8-hours post-dose at D14 for schedule A, at D10 for schedule B, at D17 forschedule C and D13 for schedule D
At each consolidation, only pre-dose at D14 of each consolidation cycle
During maintenance, only pre-dose at D14 of 2nd, 3rd and 4th maintenance cycles
Measured: 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
To describe MIDO and MIDO metabolites CPG52421 and CPG62221 at the RP2S
During induction, plasma samples will be collected at the following time points for MIDO treatment: Pre-dose, 1, 2, 4, and a last one between 6- and 8-hours post-dose at D21 of induction
At each consolidation, only pre-dose at D14 or D15 or D16 of each consolidation cycle,
During maintenance, only pre-dose at D1 of 2nd, 3rd and 4th maintenance cycles
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2027 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07726576
- Sponsor's protocol ID
- CHUBX 2024/37
- Acronym
- MIDOVEN
- Status last verified
- May 2026
- First submitted
- 29 May 2026
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07726576
- Acronym / sponsor ID
- MIDOVEN / CHUBX 2024/37
- Conditions
- Leukemia, Myeloid, Acute
- Keywords
- Acute myeloid leukemia, FLT3 mutation, midostaurin, venetoclax
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Dec 2031 (estimated)
- First posted
- 24 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Screening of 226 clinical trials on ClinTrial.gov showed 26 studies evaluating intensive chemotherapy (daunorubicin+cytarabine) and VEN but none in combination with MIDO even though 30% of patients eligible for intensive chemotherapy do receive such a regimen. Intensive chemotherapy and MIDO showed a significant median overall survival improvement but a moderate increase of patients still alive at 3 years, around an additional 10% 1. Moreover, MIDO does not allow an increase in proportion of patients in first complete remission (CR1) or CR with incomplete hematologic recovery (CRi1) after the 1st induction course. Another study with a second-generation tyrosine kinase inhibitor, quizartinib (QuANTUM-First) showed that among patients with CR1/CRi1, 42% had a measurable residual disease (MRD) <10-4 in quizartinib arm versus 38% in placebo arm, despite, here again, a significant median overall survival improvement 2. These data show that tyrosine kinase inhibitors do not increase the rate of complete remission (CR) without MRD, explaining probably the moderate improvement of definitive cure rate. The investigators hypothesize that adding VEN to this standard treatment will increase complete remission rate without MRD and improve OS of patients with FLT3-mutated AML. Two clinical trials evaluated VEN in AML patients eligible to intensive chemotherapy and showed high levels of complete remission without MRD and a manageable toxicity profile, related to VEN start date and duration of exposure 3,4. In the current study, the investigators propose the following schedule to find the best treatment sequence while preventing the risk of myelosuppression, based on available data from the two clinical trials previously presented: In schedule A, VEN will be used from D8 to D14 to harness the synergy between FLT3 and BCL2 inhibition; in schedule B, VEN will be used from D4 to D10 to harness the synergy between chemotherapy and BCL2 inhibition then between FLT3 and BCL2 inhibition. If previous schedules A and B are safe, the investigators propose to prolong VEN exposure to 10 days allowing longer association between MIDO and VEN with a schedule C with VEN from D8 to D17 and finally a schedule D with VEN from D4 to D13. Follow-up will include up to 3 consolidation courses with intermediate dose cytarabine and VEN according to previous French phase 2 clinical trial COVENIDAC 5 and MIDO in this label from D8 to D21. Finally, patients will receive 12 cycles maintenance by MIDO with VEN D1-D14 in 28-day cycles. Patients will undergo allogeneic stem cell transplantation (HSCT) according to standard indications and procedures.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Standard treatment of FLT3 mutated AML | Experimental | Drug: Venetoclax in association with 3+7 and midostaurin |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | Standard treatment of FLT3 mutated AML |
Primary outcome
Phase 1: Maximum tolerated schedule (MTS) of VEN in combination with 3+7+MIDO to define the recommended phase 2 schedule (RP2S).
Time frame: 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)
Time frame: From day 1 of induction chemotherapy up to 8 weeks
Measured by multiparameter flow cytometry (MFC) according to European Leukemia Net (ELN) 2022
32 secondary outcomes
Phase 1:Number of participants with Dose Limiting Toxicities (DLTs), Serious Adverse Events (SAEs), and Adverse Events (AEs) leading to treatment discontinuation
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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: Steady-state accumulation ratios of AUC 0-12h
Time frame: 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: Steady-state accumulation ratios of Cmax
Time frame: 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 plasma concentration-time profile from time zero to time tau (AUCtau)
Time frame: 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 extrapolated to infinity (AUCinf)
Time frame: 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: Half time (T1/2)
Time frame: 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: Oral clearance (CL/F)
Time frame: 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: Volume or volume/kg (Vz/F)
Time frame: 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 2: Number of participants experiencing at least one treatment-related adverse event, or at least one serious treatment-related adverse event
Time frame: 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 2: Number of participants experiencing at least one adverse event that led to discontinuation of treatment
Time frame: 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: Proportion of participants with complete remission (CR)/CR with incomplete hematologic recovery (CRi) without measurable residual disease (MRD)
Time frame: Day 1 of Consolidation 2, day 1 of consolidation 3 , day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, day 1 of maintenance cycle 7, day 1 of maintenance cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with complete remission (CR), CR with incomplete hematologic recovery (Cri), CR with partial hematological recovery (CRh), morphologic leukemia free state (MLFS), partial response (PR), no response, non-evaluable for response
Time frame: From day 1 of induction chemotherapy up to 8 weeks
Proportion of participants with CR/CRi/CRh without MRD
Time frame: Day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, day 1 of maintenance cycle 7, day 1 of maintenance cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi without MRD
Time frame: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi/CRh without MRD
Time frame: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi with MRD low-level (MRDLL)
Time frame: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi/CRh with MRDLL
Time frame: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi without MRD
Time frame: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Proportion of participants with CR/CRi/CRh without MRD
Time frame: From day 1 of induction chemotherapy up to 8 weeks, day 1 of Consolidation 2, day 1 of consolidation 3, day 28 of consolidation 3, day 1 of maintenance cycle 1, day 1 of maintenance cycle 4, cycle 7, cycle 10 and day 28 of maintenance cycle 12
Overall survival (OS)
Time frame: From day 1 of inclusion until the date of end of study or to the date of death from any cause
Event-free survival (EFS) and EFS including MRD relapse (RT-qPCR on NPM1 and/or NGS FLT3-ITD and/or MFC) as event (EFSMRD)
Time frame: From date of day 1 of induction chemotherapy until the date of first documented progression, including molecular progression or date of death from any cause, whichever came first, assessed up to 24 months
Relapse-free survival (RFS), and RFS including MRD relapse (RT-qPCR on NPM1 and/or NGS FLT3-ITD and/or MFC) as event (RFSMRD)
Time frame: From date of CR until the date of first documented progression, including molecular progression or date of death from any cause, whichever came first, assessed up to 24 months
Cumulative incidence of relapse (CIR), and CIR including MRD relapse (RT-qPCR on NPM1 and/or NGS FLT3-ITD and/or MFC) as event (CIRMRD)
Time frame: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
Proportion of participants with HSCT performed in CR/CRi in eligible patients
Time frame: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
Proportion of participants with HSCT performed CR/CRi/CRh in eligible patients
Time frame: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
Proportion of participants with HSCT performed in CR/CRi/CRh/MLFS in eligible patients
Time frame: From date of CR until the date of first documented progression, including molecular progression assessed up to 24 months
To describe PK of VEN
Time frame: 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
To describe MIDO and MIDO metabolites CPG52421 and CPG62221 at the RP2S
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for Leukemia, Myeloid, Acute
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Venetoclax in association with 3+7 and midostaurin in people with Leukemia, Myeloid, Acute, run by University Hospital, Bordeaux at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pierre-Yves DUMAS, PU-PH (+33 5 57 65 65 11, pierre-yves.dumas@chubordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Maximum tolerated schedule (MTS) of VEN in combination with 3+7+MIDO to define the recommended phase 2 schedule (RP2S). (time frame: From day 1 of induction chemotherapy up to 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.