Study to Improve OS in 18 to 60 Year-old Patients, Comparing Daunorubicin Versus High Dose Idarubicin Induction Regimens, High Dose Versus Intermediate Dose Cytarabine Consolidation Regimens, and Standard Versus MMF Prophylaxis of GvHD in Allografted Patients in First CR

Inclusion Criteria

• •1. Age ≥ 18 years and \< 61 years
• •2. With a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome MDS or therapy-related AML)
• •3. No prior treatment for neither AML (with the exception of hydroxyurea), nor MDS (with the exception of EPO)
• •4. ECOG performance status ≤ 3
• •5. Absence of severe uncontrolled infection
• •6. No cardiac contraindications for the use of anthracyclines : decompensated or uncontrolled heart failure, recent myocardial infarction, current signs of cardiac impairment, uncontrolled arrhythmias, LVEF (left ventricular ejection fraction) \< 50%
• •7. Total bilirubin ≤ 2 x upper limit of normal (UNL), ASAT(SGOT) and ALAT (SGPT) ≤ 2.5 X UNL, creatinine \< 150 µmol/l, unless AML-related out of range values
• •8. Genetic mutation testing of the FLT3 (FLT3-ITD ou FLT3-TKD) gene, performed in local or central laboratory
• •9. Use of appropriate methods of contraception:
• •* for patients treated with Midostaurin:
• •* women of childbearing potential should use appropriate methods of contaception throughout treatment, and for 5 months post cessation of treatment
• •* men will need to use condoms during intercourse throughout treatment, and for 5 months post cessation of treatment with Midostaurin
• •10. Patients who are covered by or beneficiaries of a social security system (Social Security or Universal Medical Coverage)
• •11. Patients who have read and understood the information sheet and signed the informed consent form
• •1. Patients enrolled in the BIG-1 trial at diagnosis
• •2. Patient presenting with AML in first CR or CRp/CRi after induction or one cycle of salvage therapy (confirmed in the 15 days preceding R4-VOS)
• •3. Favorable or intermediate risk AML patients, as stratified with BIG-1 prognostic classification
• •4. Patients randomized to R2-IDAC arm (intermediate dose cytarabine)
• •5. ECOG performance status ≤ 2
• •6. Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
• •7. Local clinical laboratory values as follows:
• •o Serum creatinine ≤ 2.0 mg/dL
• •o Total bilirubin ≤ 1.5 X the upper limit of normal (ULN)
• •* Aspartate aminotransferase (AST) ≤ 2.5 X ULN
• •* Alanine aminotransferase (ALT) ≤ 2.5 X ULN
• •8. Signed written informed consent for vosaroxin study (R4-VOS)
• •9. Women of childbearing potential must have a negative pregnancy test within 8 days before randomization R4-VOS and commit to the use of effective contraception during the period of treatment and up to 36 days after vosaroxin has been stopped. Men must use effective contraception during the treatment period and up to 96 days after vosaroxin has been stopped.
• •1. Patients enrolled in the BIG-1 trial at diagnosis
• •2. Patient presenting with AML in first CR or CRp/CRi after induction or one cycle of salvage therapy (confirmed in the 15 days preceding R4-DEX)
• •3. Favorable or intermediate risk AML patients, as stratified with BIG-1 prognostic classification
• •4. ECOG performance status ≤ 2
• •5. Local clinical laboratory values as follows:
• •* Serum creatinine ≤ 150 µmol/L
• •* Total bilirubin ≤ 1.5 X the upper limit of normal (ULN)
• •* Aspartate aminotransferase (AST) ≤ 2.5 X ULN
• •* Alanine aminotransferase (ALT) ≤ 2.5 X ULN
• •6. Signed written informed consent for dexamethasone study (R4-DEX)
• •1. Age 18 - 60 years at inclusion in BIG-1 protocol
• •2. diagnosis of AML according to WHO classification de novo or secondary to myelodysplastic syndrome (myelodysplastic syndrome must not have been treated except by ESA, Lenalidomide or non-chemotherapy) or therapy-related AML
• •3. Patients included in the BIG-1 protocol
• •4. Patients in first CR or CRp/CRi following 1 or 2 courses of induction chemotherapy according to BIG-1 protocol and who are planned to receive consolidation.
• •5. Patients stratified within the favorable and intermediate risk groups as defined by BIG-1 protocol
• •6. ECOG performance status ≤ 2
• •7. Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
• •8. Creatinine clearance ≥ 30 ml/min (calculated by the usual method of each institution), total bilirubin ≤ 1.5 times the ULN; ASAT and ALAT ≤ times the upper limit of normal (ULN)
• •9. Absence of uncontrolled infection
• •10. Women of childbearing potential must agree to use effective contraception without interruption throughout the study and for a further 3 months after the end of treatment
• •11. Written signed informed consent
• •1. Patients enrolled in the BIG-1 trial at diagnosis
• •2. Patient presenting with AML in first CR or CRp/CRi treated in the BIG-1 trial and classified in the intermediate risk group, namely:
• •* either initially favorable but poor molecular responders for NPM1 MRD: NPM1 mutation, without FLT3-ITD mutation or with an FLT3-ITD ratio \< 0.50 and MRD2 positive blood (decrease of less than 4 log from baseline at diagnosis)).
• •* Or initially favorable but requiring two cycles of chemotherapy (a salvage therapy) to obtain the first CR/CRp/CRi
• •* Or other immediate intermediaries
• •3. No metastatic or progressive cancer, with the exception of basal cell skin carcinoma and cervical carcinoma in situ
• •4. Patients with general condition preserved (ECOG ≤ 3) and with no uncontrolled severe infection
• •5. Women of childbearing age must make use of effective contraception
• •6. Patients who are covered by or beneficiaries of a social security system (Social Security or Universal Medical Coverage).
• •7. Patients who have read and understood the information sheet and signed the informed consent form