Massive AML trial aims to find best chemo and transplant protection for younger patients

NCT ID NCT02416388

Disease control Sponsor: University Hospital, Angers Source: ClinicalTrials.gov ↗

First seen Jul 17, 2026 · Last updated Jul 17, 2026

Summary

This study tests different chemotherapy doses and a drug to prevent graft-versus-host disease in adults aged 18 to 60 with newly diagnosed acute myeloid leukemia. Participants receive either idarubicin or daunorubicin during initial chemo, followed by high or intermediate doses of cytarabine. Those who get a stem cell transplant also receive either standard or mycophenolate mofetil to prevent complications. The goal is to find the best combination to improve survival.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: chemotherapy drugs (idarubicin, daunorubicin, cytarabine) and mycophenolate mofetil for GvHD prevention
What this could lead to: If successful, this could establish better chemotherapy regimens and GvHD prevention strategies, improving survival for younger AML patients.
What could go wrong: This is a large trial testing multiple approaches, so results may take years. Some treatments may not improve outcomes or could increase side effects.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2/3

Runs two stages together: whether the treatment works, then large-scale confirmation.

Participants

About 3,100 people

The number the study aims to enrol. It can still change while the study runs.

Start date

Jan 2015

Expected to finish

Jan 2032

An estimate. End dates often move.

Lead sponsor

A government agency

The lead sponsor is a government body.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 to 61 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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 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 Exclusion criteria 1.AML stratified in the unfavorable BIG-1 risk-group. 2.Diagnosis of Acute Promyelocytic Leukemia or CBF AML (ie. AML with t(8;21), t(16,16) or inv(16), or their molecular equivalents RUNX1-RUNX1T1 and CBFB-MYH11) 3.AML secondary to prior myeloproliferative disorder according to WHO classification (2008) and Philadelphia chromosome-positive AML (Ph1+) 4.Absence of CR/CRp/CRi after a maximum of two chemotherapy cycles 5.Severe medical or mental condition precluding the administration of protocol treatments 6.Prior history of cancer unless controlled for at least 2 years and except for basocellular cutaneous cancers and in situ cervix cancers 7.Positive pregnancy test 8.Breast feeding 9.Uncontrolled infection such as sepsis, or multiple organ dysfunction syndrome, uncontrolled fever 10.Documented uncontrolled fungal infection (positive blood test and cultures) 11.Prior venetoclax exposure 12.Known HBV with detectable viral load 13.Known HIV positive patients 14.Known hypersensitivity to any of the study medication 15.History of myocardial infarction, unstable angina, cerebrovascular accident (CVA) or transient ischemic attack (TIA) in the 3 months before randomization 16.Patient under hemodialysis (HD) or peritoneal dialysis (PD) 17.Concomitant treatment with cytochrome CYP3A4 inhibitor which cannot be stopped during venetoclax administration ONLY FOR PHASE 1 18.During the phase 2, for patients randomized in the IDAC + Venetoclax arm, if concomitant treatment with cytochrome CYP3A4 inhibitor cannot be stopped, a dose reduction of 70% of venetoclax must be apply \-------------------------------------- For randomization R3 (before AlloHSCT): Inclusion criteria 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 Exclusion criteria 1. Complete remission is not obtained (CR, CRp/CRi) after induction and/or salvage therapy 2. Patient presenting with AML in first CR or CRp/CRi treated in the BIG-1 trial and classified either in the favorable risk group or the unfavorable risk group 3. Patients with a severe organ or psychiatric pathology, presumed to be independent of AML and contraindicating the allograft 4. Patients who, for family, social or geographic reasons, do not wish to be regularly monitored via consultation 5. Uncontrolled severe infection at the time of inclusion 6. Serology positive for HIV 1 or 2 or HTLV 1 or 2, or active HBV or HCV viral infection 7. Pregnant women (beta-HCG positive) or currently breastfeeding 8. Adult patient who is incapacitated, under wardship, legal guardianship, or under the protection of the courts 9. Patients under State Medical Assistance (AME)

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Conditions

The condition(s) this trial relates to.

acute myeloid leukemia

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Acute myeloid leukemia (AML)

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

55 sites. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

CH Amiens Hôpital Sud
RECRUITING

Amiens, France
CH Beziers
RECRUITING

Béziers, France
CH Bordeaux
RECRUITING

Bordeaux, France
CH Caen
RECRUITING

Caen, France
CH Dunkerque
RECRUITING

Dunkirk, France
CH Hôtel Dieu
RECRUITING

Nantes, France
CH Lens
RECRUITING

Lens, France
CH Lyon Sud
RECRUITING

Lyon, France
CH Meaux
RECRUITING

Meaux, France
CH Mulhouse
RECRUITING

Mulhouse, France
CH Pontchaillou
RECRUITING

Rennes, France
CH Valenciennes
RECRUITING

Valenciennes, France
CH Versailles
RECRUITING

Le Chesnay, France
CH Victor Dupouy
RECRUITING

Argenteuil, France
CHR Metz Thionville_Hôpital de Mercy
RECRUITING

Metz, France
CHRU de Lille, Hôpital Huriez
RECRUITING

Lille, France
CHRU de Nîmes
RECRUITING

Nîmes, France
CHU Angers
RECRUITING

Angers, 49100, France
CHU Bretonneau
RECRUITING

Tours, France
CHU Estaing
RECRUITING

Clermont-Ferrand, France
CHU Nice
RECRUITING

Nice, France
CHU de Dijon
RECRUITING

Dijon, France
CHU de Limoges
RECRUITING

Limoges, France
CHU de Poitiers
RECRUITING

Poitiers, France
Centre Antoine Lacassagne
RECRUITING

Nice, France
Centre Henri Becquerel
RECRUITING

Rouen, France
Centre Hospitalier René Dubos
RECRUITING

Cergy-Pontoise, France
Centre Hospitalier Saint Jean
RECRUITING

Perpignan, France
Centre Hospitalier Sud Francilien
RECRUITING

Corbeil-Essonnes, France
Centre Hospitalier de la Côte Basque
RECRUITING

Bayonne, France
Centre Leon Berard (CLB)
RECRUITING

Lyon, France
Clinique du parc
WITHDRAWN

Castelnau-le-Lez, 34170, France
HIA Percy
RECRUITING

Clamart, France
Hopital Victor Provo
RECRUITING

Roubaix, France
Hôpital Avicenne
RECRUITING

Bobigny, France
Hôpital Cochin
RECRUITING

Paris, France
Hôpital Hautepierre
RECRUITING

Strasbourg, France
Hôpital Henri Mondor
RECRUITING

Créteil, France
Hôpital Jean Minjoz
RECRUITING

Besançon, France
Hôpital La Pitié Salpêtrière
RECRUITING

Paris, France
Hôpital Michallon
RECRUITING

Grenoble, France
Hôpital Morvan
RECRUITING

Brest, France
Hôpital Necker Enfants Malades
RECRUITING

Paris, France
Hôpital René Huguenin
RECRUITING

Saint-Cloud, France
Hôpital Robert Debré
RECRUITING

Reims, France
Hôpital Saint Antoine
RECRUITING

Paris, France
Hôpital Saint Eloi
RECRUITING

Montpellier, France
Hôpital St Louis
RECRUITING

Paris, France
Hôpital St Vincent de Paul
RECRUITING

Lille, France
Hôpital du Dr Duchenne
RECRUITING

Boulogne-sur-Mer, France
Hôpitaux de Brabois_CHU Nancy
RECRUITING

Vandœuvre-lès-Nancy, France
IUCT Toulouse
RECRUITING

Toulouse, France
Institut Paoli Calmettes
RECRUITING

Marseille, France
Institut de Cancérologie Gustave Roussy
RECRUITING

Villejuif, France
Institut de Cancérologie Lucien Neuwirth
RECRUITING

Saint-Priest-en-Jarez, France
Marseille La Conception
RECRUITING

Marseille, 13005, France

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