Venetoclax Added to Standard Chemotherapy and Midostaurin for Patients with FLT3-Mutated Acute Myeloid Leukemia Eligible for Intensive Chemotherapy

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What is this study about?

This clinical trial is studying Acute Myeloid Leukemia with a FLT3 mutation, a change in the leukemia cells that can help the cancer grow. The purpose of the study is to find the safest way to add venetoclax to standard treatment with 3+7 chemotherapy and midostaurin during the first part of treatment, called induction, and to see how well this treatment plan works. Venetoclax is a tablet taken by mouth.

The study treatment uses three medicines together: venetoclax, standard 3+7 chemotherapy, and midostaurin. Treatment is given in stages. First comes induction treatment to try to bring the leukemia under control. After that, some participants may continue with more treatment, called consolidation, and later some may receive maintenance treatment to help keep the leukemia from coming back. In some cases, a stem cell transplant, also called HSCT, may be part of the care plan. The study follows participants through these treatment phases and checks for side effects and other health changes.

This is a Phase 1/2 study, which means it is an early study designed to find the best dose schedule and learn more about safety. It also looks at how many participants have no clear signs of leukemia left after treatment. The study is planned to run over several years.

1 induction treatment

After you join the study, you receive venetoclax by mouth as a film-coated tablet. The study uses this medicine together with the standard 3+7 treatment and midostaurin during the first treatment phase, called induction.

The purpose of this phase is to find the highest schedule of venetoclax that can be given with 3+7+midostaurin during induction, and to select the dose schedule for the next phase of the study.

During this phase, the study checks for DLTs, which means dose-limiting toxicities. These are side effects severe enough to limit the planned treatment.

2 response check after induction

After induction treatment, your blood and bone marrow response is checked as soon as possible after your blood counts recover, or up to day 56.

The study looks for CR or CRi without MRD. CR means complete remission, which is when the signs of leukemia are no longer found. CRi means complete remission with incomplete blood count recovery. MRD means minimal residual disease, which is a very small amount of leukemia that may remain after treatment.

The response is measured by MFC, which means multiparameter flow cytometry, a test that examines cells in the blood or bone marrow. The study uses the ELN 2022 rules, which are a standard set of criteria for judging treatment response.

3 consolidation treatment

If you continue in the study, you may receive further treatment in consolidation phases after induction.

The study assesses your response after consolidation 1, consolidation 2, and consolidation 3.

At each of these time points, the study checks whether you have CR, CRi, or CRh without MRD. CRh means complete remission with partial recovery of blood counts.

The study also checks for MRD low-level, which means a very small remaining amount of leukemia that is still detectable at a low level.

In some patient groups, the study also uses RT-qPCR, which means a laboratory test that measures specific leukemia-related genetic changes, and NGS, which means next-generation sequencing, another test used to look for leukemia-related changes.

4 stem cell transplant phase

If you are eligible, the study may include HSCT, which means hematopoietic stem cell transplantation. This is a stem cell transplant used to restore blood-forming cells.

The study records whether the transplant is performed while you are in CR, CRi, CRh, or MLFS. MLFS means morphologic leukemia-free state, which is a state where no clear leukemia is seen under the microscope.

After this phase, the study checks response again according to the planned study schedule.

5 maintenance treatment

If you continue in the study, you may receive maintenance treatment after the earlier phases.

The study checks your response after maintenance 3, maintenance 6, maintenance 9, and maintenance 12.

At these time points, the study looks for CR, CRi, CRh, and MRD status. In some patient groups, the study also checks RT-qPCR on NPM1 and NGS on FLT3.

The study also records adverse events, which are unwanted medical problems, and serious adverse events, which are more serious unwanted medical problems, during maintenance.

6 study follow-up and outcome recording

The study records how long patients stay alive from day 1 of inclusion until death from any cause, if this occurs.

The study also records event-free survival, relapse-free survival, and cumulative incidence of relapse. These measures track whether the disease returns or another study-defined event happens.

The study follows treatment results and side effects during induction, consolidation, and maintenance.

Who Can Join the Study?

Be 18 to 70 years old.
Have newly diagnosed acute myeloid leukemia (AML) based on the 2022 World Health Organization (WHO) classification.
Have a documented FLT3 gene mutation, which means a change in the FLT3 gene. This can be FLT3-ITD, FLT3-TKD D835, FLT3-TKD I836, or more than one of these.
For FLT3-ITD, the test must show an ITD/wild-type ratio of at least 0.05 (5%). Wild-type means the normal form of the gene.
For FLT3-TKD D835 or I836, the test must show a variant allele frequency (VAF) greater than 5%. VAF means the share of blood or bone marrow cells carrying the mutation.
Be able to receive intensive chemotherapy, which means strong cancer treatment given in the hospital or under close medical supervision.
Have an ECOG performance status of 0 to 2, meaning the person is fully active, has only mild limits, or is able to care for themselves but cannot do heavy work.
Have adequate liver function, meaning bilirubin is 1.5 times the upper limit of normal or lower and AST and ALT are 2.5 times the upper limit of normal or lower, unless the higher values are due to leukemia in the liver. Bilirubin, AST, and ALT are blood tests that show how well the liver is working.
Have adequate kidney function, meaning an estimated glomerular filtration rate (eGFR) greater than 50 mL/min. eGFR is a blood test estimate of how well the kidneys filter waste.
Have signed written informed consent, meaning the patient has agreed in writing to join the study after receiving the study information.
Be affiliated with the French social security system, meaning having the required health insurance coverage.
If male and having a female partner who could become pregnant, agree to use contraception starting at screening and continue during the study and for 120 days after the last study drug dose.
If male, agree not to donate sperm starting at screening, during the study, and for 120 days after the last study drug dose.
If female, be not pregnant and either not able to become pregnant or agree to use contraception starting at screening, during the study, and for 180 days after the last study drug dose. Not able to become pregnant means being post-menopausal (at least 1 year without periods) or surgically sterile (unable to have children because of surgery done at least 1 month before screening).
If female, agree not to breastfeed starting at screening, during the study, and for 60 days after the last study drug dose.
If female, agree not to donate eggs (ova) starting at screening, during the study, and for 180 days after the last study drug dose.

Who Cannot Join the Study?

Having received anti-leukemia treatment within 14 days before the first study dose, including demethylating agents (drugs that help change how genes work in cancer cells). Hydroxyurea is allowed if it is only being used to control leukemia cells in the blood.
Having a serious medical condition that the study doctor thinks could make the risk of death from the intensive chemotherapy too high.
Having another cancer that is likely to affect treatment safety or the study procedures, except for certain allowed cancers listed below.
Testing positive for HIV because of possible interactions with study drugs.
Having active hepatitis B or hepatitis C that is not controlled. Hepatitis is a liver infection caused by a virus.
Having a heart pumping function, called ejection fraction, below 45%. This means the heart is not pumping enough blood with each beat.
Having taken certain medicines within 7 days before study treatment, including strong CYP3A inducers such as rifampicin, carbamazepine, phenytoin, or St. John’s wort. These are drugs that can make the body break down study medicines too quickly.
Using warfarin, or needing to use it. Warfarin is a blood thinner, and it may interact with the study drugs.
Having taken certain medicines within 5 days before study treatment called CYP3A inhibitors such as fluconazole, ketoconazole, or clarithromycin. These are drugs that can make the body break down study medicines too slowly.
Needing to take other medicines that are strong inhibitors or inducers of P-gp unless they are absolutely necessary. P-gp is a body transport system that helps move medicines in and out of cells.
Eating grapefruit, Seville oranges, or starfruit, or products made from them, within 3 days before study treatment.
Having a history of other cancers before joining the study, except for: in situ breast or cervix cancer that was treated well, basal cell skin cancer, localized squamous cell skin cancer, or a past cancer treated more than 2 years ago with no sign of active disease. In situ means very early cancer that has not spread.
Having had prior treatment for AML or MDS. AML means acute myeloid leukemia, and MDS means myelodysplastic syndrome, a bone marrow disorder.
Having any other serious medical problem, abnormal lab result, or mental health condition that could make participation unsafe or prevent the person from giving informed consent (a clear agreement to join the study after understanding it).
Having a severe medical or mental condition that makes it impossible to receive the study treatment as planned.
Being deprived of liberty by a court or administrative decision, being under legal protection such as guardianship or curatorship, or being under psychiatric care.
Having another health problem that the doctor thinks would not be compatible with intensive chemotherapy, unless the study medical monitor reviews and approves it before enrollment.
Having a known allergy or sensitivity to any study medicine.
Having leukemia in the central nervous system (the brain and spinal cord).
Having had VEN or another BCL2 inhibitor before. BCL2 inhibitors are drugs that help kill leukemia cells by blocking a survival protein.
Having had anthracycline treatment before for another cancer. Anthracyclines are a group of chemotherapy drugs.
Having AML that developed from another blood disorder, including myelodysplastic syndrome, myeloproliferative disorders (conditions where the bone marrow makes too many blood cells), or therapy-related AML (leukemia caused by previous cancer treatment).
Having acute promyelocytic leukemia, CBF-AML (a specific AML type with a certain chromosome change), or Phi+ AML (AML with the Philadelphia chromosome).
Having serious active heart disease within 6 months before study treatment, or having a QTcF of 450 milliseconds or more. QTcF is a heart rhythm measurement on an electrocardiogram.
Having a history of Long QT Syndrome, a condition that can cause dangerous heart rhythm problems.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France
Oncopole Claudius Regaud	Toulouse	France

Other Sites

Site Name	City	Country	Status
Centre Hospitalier De La Cote Basque	Bayonne	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	01.06.2026

Trial locations

Investigated drugs:

Venetoclax

Venetoclax is an oral cancer medicine being tested in this trial. It is added to standard induction treatment to help kill leukemia cells in people with FLT3-mutated acute myeloid leukemia. The study is looking at the best way to give venetoclax together with the other treatment and to see how well this combination works after the first round of chemotherapy.

Midostaurin is a targeted cancer medicine taken by mouth that is used with standard chemotherapy for patients whose leukemia has a FLT3 mutation. In this trial, it is part of the usual induction treatment and is being given together with other medicines to help attack the leukemia cells more effectively.

3+7 chemotherapy is the standard induction chemotherapy used to treat acute myeloid leukemia. It is a treatment plan made up of two chemotherapy medicines given over several days to try to bring the leukemia into remission by destroying as many cancer cells as possible.

Investigated diseases:

Acute myeloid leukaemia

FLT3-mutated acute myeloid leukemia – A fast-growing cancer of the blood and bone marrow in which the body makes too many abnormal myeloid cells. In the FLT3-mutated form, the leukemia cells have a change in the FLT3 gene that helps them grow and divide more quickly. As the disease progresses, these abnormal cells crowd out normal blood cells in the bone marrow and can spread into the blood and other tissues.

Trial ID:

2024-517130-17-00

Protocol code:

CHUBX 2024/37

Trial Phase:

Human Pharmacology (Phase I) – Other

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Venetoclax Added to Standard Chemotherapy and Midostaurin for Patients with FLT3-Mutated Acute Myeloid Leukemia Eligible for Intensive Chemotherapy

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?