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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

RecruitingPhase 2, Phase 3Ages 18 Years - 61 YearsAllUniversity Hospital, Angers
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In plain words

What the trial is, and whether it could suit you

This open label, multicenter phase II/III study with multiple randomization phases at differents stages of AML treatment (induction, consolidation and HSCT where applicable) is designed to improve OS in younger (18 to 60 year-old) patients, with AML risk-adapted patient strategies. Within the intermediate risk AML group, optimal GvHD prophylaxis following allogeneic SCT in first CR, after either myeloablative (MAC) or reduced intensity (RIC) conditioning, will also be evaluated. With an adaptative design, this clinical trial could test up to 3 novel AML agents of interest.

Sign in to get the eligibility rules as simple questions to take to your doctor.

📋 Eligibility rules (as published)
Inclusion Criteria (at diagnosis) : 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 Exclusion criteria (at diagnosis) : 1.Patients with acute promyelocytic leukemia (APL), as confirmed either by t(15;17) or by the presence of PML-RARA fusion transcripts 2.Patients with core binding factor (CBF) AML, as confirmed either by t(8;21), t(16,16) or inv(16), or by fusion transcripts resulting from these cytogenetic abnormalities (RUNX1-RUNX1T1, CBFB-MYH11). 3.Patients with secondary AML arising from myeloproliferative disorders previously known according to the 2008 WHO classification 4.Patients with Ph1+ AML or previous Ph1+ disorder (chronic myelogenous leukemia) 5.Severe psychiatric or organic disorder, supposed to be independent from AML, that would contraindicate treatment, including allogeneic HSCT 6.No psychological, familial, social, or geographic reason that would compromise clinical follow up 7.History of uncontrolled cancer for the last 2 years, with the exception of basal cell carcinoma or carcinoma in situ of the cervix 8.Uncontrolled severe infection 9.Patients with positive serology for HIV-1 and -2, or HTLV -1 and -2, or active hepatitis virus B or C infection 10.Pregnant or lactating women 11.Legal incapacity (patients under tutorship, curatorship or judicial protection) \------------------------------------------ For randomization R4-VOS (post-induction/salvage) : Inclusion criteria 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. Exclusion criteria 1.Patients classified in the unfavorable risk group according to the BIG-1 protocol classification 2.Complete remission is not attained (CR, CRp/CRi) after induction and/or salvage therapy 3.Positive pregnancy test 4.Severe uncontrolled infection such as sepsis, or multiple organ dysfunction syndrome, uncontrolled fever 5.Documented uncontrolled fungal infection (positive blood test and cultures) 6.History of myocardial infarction, unstable angina, cerebrovascular accident (CVA) or transient ischemic attack (TIA) in the 3 months before randomization 7.Patient under hemodialysis (HD) or peritoneal dialysis (PD) \------------------------------------------ For randomization R4-DEX (post-induction/salvage) : Inclusion criteria 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) Exclusion criteria 1.Severe uncontrolled infection such as sepsis, or multiple organ dysfunction syndrome, uncontrolled fever 2.Documented uncontrolled fungal infection (positive blood test and cultures 3.History of myocardial infarction, unstable angina, cerebrovascular accident (CVA) or transient ischemic attack (TIA) in the 3 months before randomization 4.Patient under hemodialysis (HD) or peritoneal dialysis (PD) \-------------------------------------- For randomization R4-VEN (post-induction/salvage) : Inclusion criteria 1. Age 18 - 60 years at incl
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What it tests

  • Idarubicin
  • Daunorubicin
  • HD Cytarabine
  • Cyclosporine
  • Methotrexate
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Where

56 sites
CH Amiens Hôpital Sud
Amiens, France
CHU Angers
Angers, France
CH Victor Dupouy
Argenteuil, France
Centre Hospitalier de la Côte Basque
Bayonne, France
Hôpital Jean Minjoz
Besançon, France
CH Beziers
Béziers, France
Hôpital Avicenne
Bobigny, France
CH Bordeaux
Bordeaux, France

…and 48 more on ClinicalTrials.gov.

🤝 Taking part is your choice, and you can leave at any time. Only the trial team can confirm you are eligible — always decide together with your own doctor.
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