VENETOCLAX for Acute myeloid leukemia

Inclusion criteria

• {"criterion_text":"- Patients aged 18 and over but under 61 years old\n- Patients with AML, de novo or secondary to myelodysplastic syndrome or cancer therapy (\"therapy-related\" AML)\n- Not previously treated for AML (except hydroxyurea) or MDS (except with EPO)\n- General condition maintained (ECOG performance scale ≤ 3)\n- No severe uncontrolled infection\n- No cardiac contraindications from the use of anthracyclines (decompensated or uncontrolled coronary insufficiency, recent myocardial infarction, current manifestations of cardiac insufficiency, uncontrolled rhythm disorders, ventricular ejection fraction < 50%)\n- AST and ALAT ≤ 2.5 times upper limit of normal (ULN), total bilirubin ≤ 2 times ULN, creatinine < 150 μmol/L unless these biological abnormalities are related to leukemia\n- Search for FLT3 gene mutations(FLT3-ITD or FLT3-TKD), in a local or centralized laboratory\n- Use of an effective contraceptive method\n- Women of childbearing potential should use an effective method of contraception for the duration of treatment and up to 5 months after discontinuation of treatment\n- Men should use condoms during sexual intercourse, for the duration of treatment and up to 5 months after stopping midostaurin.\n- Patients who are members or beneficiaries of a social security scheme\n- Having read and understood the information letter and signed the informed consent form\n- Patient included in the BIG-1 protocol\n- Patient with AML in CR or CRp/CRi after induction or salvage therapy for randomized phase 2 (confirmed within 15 days prior to R4-VEN randomization)\n- Patient classified in the favorable or intermediate risk group according to the prognostic classification of the BIG-1 protocol\n- General condition maintained (ECOG performance scale ≤ 2)\n- Creatinine ≤ 150 μmol/L, total bilirubin ≤ 1.5 X ULN; AST and ALAT ≤ 2.5 times upper limit of normal (ULN)\n- Signed the specific consent for the venetoclax study\n- LVEF ≥ 40%\n- No severe uncontrolled infection\n- Women of childbearing potential must have uninterrupted effective contraception during the study and for at least 3 months after the end of treatment"}

Exclusion criteria

• {"criterion_text":"- Patients with acute promyelocytic leukemia (AML3) with either t(15;17) or a positive test for the PML-RARA transcript, or AML in the CBF group with either t(8;21), t(16,16) or inv(16), or a positive test for the transcripts associated with these cytogenetic abnormalities (RUNX1-RUNX1T1, CBFB-MYH11).\n- Patients with AML secondary to a previously known myeloproliferative syndrome according to 2008 WHO classification\n- Patients with previous Philadelphia chromosome (Ph1+) AML or chronic myeloid leukemia\n- Patients with severe organic or psychiatric pathology presumed to be independent of AML and contra-indicating treatment, including allogeneic transplantation\n- Patients who, for psychological, family, social or geographical reasons, are unable to receive regular consultation services\n- Previous cancer, if uncontrolled for at least two years, with the exception of basal cell skin carcinoma and carcinoma in situ of the uterine cervix\n- No severe uncontrolled infection at the time of inclusion\n- Positive serology for HIV 1 or 2 or HTLV 1 or 2, or active hepatitis B or C infection\n- Pregnant (beta-hCG positive) or breast-feeding women\n- Looked-after adult patients who are under guardianship\n- Patient on State Medical Aid\n- Patient classified in the unfavorable risk group according to BIG-1 protocol classification\n- Patient included in R4-DEX\n- Uncontrolled severe infection such as sepsis, or multi-organ failure syndrome, uncontrolled fever\n- Documented, uncontrolled fungal infection (positive blood and cultures)\n- Previous myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 3 months prior to randomization\n- Patient on hemodialysis (HD) or peritoneal dialysis (PD)\n- Any severe, uncontrolled condition including diabetes, hypertension, gastric ulcer, psychiatric disorders, myasthenia gravis or glaucoma\n- Pregnant (beta-hCG positive) or breast-feeding women\n- Patients previously treated with venetoclax\n- Active hepatitis B viral infection\n- Patient known to be HIV positive\n- Known hypersensitivity to any of the study drugs.\n- Concomitant treatment with a CYP3A4 inhibitor that cannot be stopped during phase 1 administration of venetoclax only.\n- During the randomized phase 2, in the case of IDAC + venetoclax randomized paients, if concomitant treatment with a CYP3A4 inhibitor cannot be stopped, the venetoclax dose will need to be reduced by 75%."}

Primary endpoints

• {"endpoint_text":"- For R1 and R2 randomizations: The primary endpoint will be a comparison of overall survival (OS) at 3 years according to the treatment considered (idarubicin vs. daunorubicin for randomization 1, and high-dose cytarabine 3.0 g/m2 vs. intermediate-dose cytarabine 1.5 g/m2 for randomization 2).\n- For R3 randomization: The primary endpoint will be the cumulative incidence of grade II to IV acute GvHD at D100, compared according to the GvHD prophylaxis regimen considered (standard regimen or mycopheno","definition_or_measurement_approach":"R1/R2: Overall survival (OS) at 3 years (time-to-event measure of survival up to 3 years). R3: Cumulative incidence of grade II-IV acute graft-versus-host disease at Day 100 (incidence assessed at D100 using grade II–IV aGvHD criteria)."}

France

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

478

Number Of Participants

3100

Primary sponsor

Full Name

Centre Hospitalier Universitaire D'Angers

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France