Acute Myeloid Leukemia (AML)Phase 2/3BIG-1NCT02416388
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
A Phase 2/3 study testing Idarubicin, Daunorubicin and HD Cytarabine in people with Acute Myeloid Leukemia (AML), run by University Hospital, Angers at 56 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 61 years
- Conditions the study is for
- Acute Myeloid Leukemia (AML)
- What is being tested?
- Idarubicin, Daunorubicin and HD Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,100 participants
- Where
- 56 sitesFrance
- Study dates
- Jan 2015to Jan 2032
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 61 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age ≥ 18 years and < 61 years
- With a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome MDS or therapy-related AML)
- No prior treatment for neither AML (with the exception of hydroxyurea), nor MDS (with the exception of EPO)
- ECOG performance status ≤ 3
- Absence of severe uncontrolled infection
- 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%
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- 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
- Genetic mutation testing of the FLT3 (FLT3-ITD ou FLT3-TKD) gene, performed in local or central laboratory
- 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
- Patients who are covered by or beneficiaries of a social security system (Social Security or Universal Medical Coverage)
- Patients who have read and understood the information sheet and signed the informed consent form
- Patients enrolled in the BIG-1 trial at diagnosis
- 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)
- Favorable or intermediate risk AML patients, as stratified with BIG-1 prognostic classification
- Patients randomized to R2-IDAC arm (intermediate dose cytarabine)
- ECOG performance status ≤ 2
- Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
- 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
- Signed written informed consent for vosaroxin study (R4-VOS)
- 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.
- Patients enrolled in the BIG-1 trial at diagnosis
- 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)
- Favorable or intermediate risk AML patients, as stratified with BIG-1 prognostic classification
- ECOG performance status ≤ 2
- 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
- Signed written informed consent for dexamethasone study (R4-DEX)
- Age 18 - 60 years at inclusion in BIG-1 protocol
- 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
- Patients included in the BIG-1 protocol
- 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.
- Patients stratified within the favorable and intermediate risk groups as defined by BIG-1 protocol
- ECOG performance status ≤ 2
- Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
- 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)
- Absence of uncontrolled infection
- 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
- Written signed informed consent
- Patients enrolled in the BIG-1 trial at diagnosis
- 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
- No metastatic or progressive cancer, with the exception of basal cell skin carcinoma and cervical carcinoma in situ
- Patients with general condition preserved (ECOG ≤ 3) and with no uncontrolled severe infection
- Women of childbearing age must make use of effective contraception
- Patients who are covered by or beneficiaries of a social security system (Social Security or Universal Medical Coverage).
- Patients who have read and understood the information sheet and signed the informed consent form
Who cannot join
- 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) :
- 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)
- ------------------------------------------
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- For randomization R4-DEX (post-induction/salvage) :
- 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) :
- 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):
- Complete remission is not obtained (CR, CRp/CRi) after induction and/or salvage therapy
- 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
- Patients with a severe organ or psychiatric pathology, presumed to be independent of AML and contraindicating the allograft
- Patients who, for family, social or geographic reasons, do not wish to be regularly monitored via consultation
- Uncontrolled severe infection at the time of inclusion
- Serology positive for HIV 1 or 2 or HTLV 1 or 2, or active HBV or HCV viral infection
- Pregnant women (beta-HCG positive) or currently breastfeeding
- Adult patient who is incapacitated, under wardship, legal guardianship, or under the protection of the courts
- Patients under State Medical Assistance (AME)
Trial locations and contacts
56 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Mathilde Hunault, PD contact
56 sites in 1 country
France56 sites, 55 recruiting
- Recruiting
CH Amiens Hôpital Sud
Amiens
Jean-Pierre Marolleau
- Recruiting
CHU Angers
Angers, 49100
Mathilde Hunault, MaHunault@chu-angers.fr
- Recruiting
CH Victor Dupouy
Argenteuil
Ahmad Al Jijakli, ahmadkanj.aljijakli@ch-argenteuil.fr
- Recruiting
Centre Hospitalier de la Côte Basque
Bayonne
Anne Banos
- Recruiting
Hôpital Jean Minjoz
Besançon
Fabrice Larosa
- Recruiting
CH Beziers
Béziers
Alain Saad, alain.saad@ch-beziers.fr
- Recruiting
Hôpital Avicenne
Bobigny
Claude Gardin
- Recruiting
CH Bordeaux
Bordeaux
Arnaud Pigneux
- Recruiting
Hôpital du Dr Duchenne
Boulogne-sur-Mer
Bachra Choufi
- Recruiting
Hôpital Morvan
Brest
Gaelle Guillerm, gaelle.guillerm@chu-brest.fr
- Recruiting
CH Caen
Caen
Sylvain Chantepie
- Withdrawn
Clinique du parc
Castelnau-le-Lez, 34170
- Recruiting
Centre Hospitalier René Dubos
Cergy-Pontoise
Ioana Vaida, ioana.vaida@ch-pontoise.fr
- Recruiting
HIA Percy
Clamart
Jean-Valère Malfuson
- Recruiting
CHU Estaing
Clermont-Ferrand
Aurelie Ravinet, aravinet@chu-clermontferrand.fr
- Recruiting
Centre Hospitalier Sud Francilien
Corbeil-Essonnes
Celia Salanoubat, celia.salanoubat@ch-sud-francilien.fr
- Recruiting
Hôpital Henri Mondor
Créteil
- Recruiting
CHU de Dijon
Dijon
Denis Caillot, denis.caillot@chu-dijon.fr
- Recruiting
CH Dunkerque
Dunkirk
Maxime Bemba
- Recruiting
Hôpital Michallon
Grenoble
Jean-Yves Cahn
- Recruiting
CH Versailles
Le Chesnay
Philippe Rousselot
- Recruiting
CH Lens
Lens
Laure STALNIKIEWICZ, lstalnikiewicz@ch-lens.fr
- Recruiting
CHRU de Lille, Hôpital Huriez
Lille
Bruno Quesnel, bruno.quesnel@chru-lille.fr
- Recruiting
Hôpital St Vincent de Paul
Lille
Nathalie Cambier
- Recruiting
CHU de Limoges
Limoges
Pascal Turlure
- Recruiting
Centre Leon Berard (CLB)
Lyon
Amine Belhabri, amine.belhabri@lyon.unicancer.fr
- Recruiting
CH Lyon Sud
Lyon
Xavier Thomas
- Recruiting
Marseille La Conception
Marseille, 13005
Régis COSTELLO, PD, +33491384150, regis.costello@ap-hm.fr
- Recruiting
Institut Paoli Calmettes
Marseille
Norbert Vey
- Recruiting
CH Meaux
Meaux
Jamilé Frayfer
- Recruiting
CHR Metz Thionville_Hôpital de Mercy
Metz
Veronique Dorvaux, v.dorvaux@chr-metz-thionville.fr
- Recruiting
Hôpital Saint Eloi
Montpellier
Yosr Hicheri
- Recruiting
CH Mulhouse
Mulhouse
Mario Ojeda-Uribe
- Recruiting
CH Hôtel Dieu
Nantes
Pierre Peterlin
- Recruiting
Centre Antoine Lacassagne
Nice
Lauris Gastaud
- Recruiting
CHU Nice
Nice
Thomas Cluzeau
- Recruiting
CHRU de Nîmes
Nîmes
Eric Jourdan, eric.jourdan@chu-nimes.fr
- Recruiting
Hôpital Cochin
Paris
Didier Bouscary
- Recruiting
Hôpital La Pitié Salpêtrière
Paris
Madalina Uzunov
- Recruiting
Hôpital Necker Enfants Malades
Paris
Felipe Suarez
- Recruiting
Hôpital Saint Antoine
Paris
Ollivier Legrand, ollivier.legrand@sat.aphp.fr
- Recruiting
Hôpital St Louis
Paris
Emmanuel Raffoux
- Recruiting
Centre Hospitalier Saint Jean
Perpignan
Laurence Sahnes, laurence.sahnes@ch-perpignan.fr
- Recruiting
CHU de Poitiers
Poitiers
Maria Pilar Gallego-Hernanz
- Recruiting
Hôpital Robert Debré
Reims
Chantal Himberlin, chimberlin@chu-reims.fr
- Recruiting
CH Pontchaillou
Rennes
Marc Bernard
- Recruiting
Hopital Victor Provo
Roubaix
Isabelle Plantier
- Recruiting
Centre Henri Becquerel
Rouen
Emilie Lemasle
- Recruiting
Hôpital René Huguenin
Saint-Cloud
Jacques Vargaftig
- Recruiting
Institut de Cancérologie Lucien Neuwirth
Saint-Priest-en-Jarez
Emmanuelle Tavernier
- Recruiting
Hôpital Hautepierre
Strasbourg
Bruno Lioure
- Recruiting
IUCT Toulouse
Toulouse
Christian Recher
- Recruiting
CHU Bretonneau
Tours
Emmanuel Gyan, emmanuel.gyan@univ-tours.fr
- Recruiting
CH Valenciennes
Valenciennes
Jose Fernandes
- Recruiting
Hôpitaux de Brabois_CHU Nancy
Vandœuvre-lès-Nancy
Gabrielle Roth-Guepin, g.roth-guepin@chu-nancy.fr
- Recruiting
Institut de Cancérologie Gustave Roussy
Villejuif
Stephane De Botton
About this study
Official title: Phase II/III Randomized Study to Improve Overall Survival 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 Mycophenolate Mofetil Prophylaxis of Graft Versus Host Disease in Allografted Patients in First CR : a Backbone InterGroup-1 Trial
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.
- Conditions
- Acute Myeloid Leukemia (AML)
- Being tested
- Idarubicin, Daunorubicin, HD Cytarabine, Cyclosporine, Methotrexate
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IdarubicinDrug
Induction chemotherapy :
Idarubicin 9mg/m² /day, from D1 to D5 (IV, 30min)
+ cytarabine 200mg/m²/day from D1 to D7 (IV 24 h)
Bone marrow aspirate on D15 : if medullary blasts rate < 5% → G-CSF (5 μg/kg/day) until hematopoietic recovery (PNN ≥ 1 G/L).
DaunorubicinDrug
Induction chemotherapy :
Daunorubicin 90mg/m²/day, from D1 to D3 (IV, 30min)
+ cytarabine 200mg/m² /day from D1 to D7 (IV 24 h)
Bone marrow aspirate on D15 : if medullary blasts rate < 5% → G-CSF (5 μg/kg/day) until hematopoietic recovery (PNN ≥ 1 G/L).
HD CytarabineDrug
Consolidation chemotherapy course (s) :
-High dose cytarabine: 3g/m² /12h on D1, D3 and D5
For all patients, G-CSF (5 μg/kg/day) : SC or IV (30 min) from D8 until hematopoietic recovery (PNN ≥ 1 G/L)
Up to 3 consolidation courses, depending on the patient AML risk group
CyclosporineDrug
GvHD prophylaxis post allogeneic SCT :
-Cyclosporine : 3 mg/kg /day from D-1 (IV) or 6 mg/kg/day from D-3 (PO). Not to be stopped before D100
MethotrexateDrug
GvHD prophylaxis post allogeneic SCT :
-15 mg/m² on D+1 then 10 mg/m² on D+3, D+6 and D+11
Mycophenolic acid (MPA)Drug
GvHD prophylaxis post allogeneic SCT :
- 720 mg BID from D0 to D+28 for HLA-identical siblings
- 720 mg BID from D0 to D+45 for 10/10 HLA allele-matched unrelated donors
vosaroxinDrug
Consolidation chemotherapy course (s) :
-70 mg/m² on D1 and D4
ID cytarabineDrug
Consolidation chemotherapy course (s) :
-Intermediate dose cytarabine: 1.5g/m² /12h on D1, D3 and D5
For all patients, G-CSF (5 μg/kg/day) : SC or IV (30 min) from D8 until hematopoietic recovery (PNN ≥ 1 G/L)
Up to 3 consolidation courses, depending on the patient AML risk group
DexamethasoneDrug
Consolidation chemotherapy course (s) :
-10 mg/12h on D1, D3 and D5
VenetoclaxDrug
Consolidation chemotherapy course (s) :
Once RP2D has been determined from the results of the dose selection phase (phase 1), the optimal dose level retained for randomized phase 2 will be one of the following:
- 100 mg/d on D1 to D8 (selection phase dose level 1)
- or 200 mg/d on D1 to D8 (selection phase dose level 2)
- or 400 mg/d on D1 to D8 (selection phase dose level 3)
- or 400 mg/d on D1 to D14 (selection phase dose level 4)
| Study group | Role | What they receive |
|---|---|---|
| R1-IDA | Experimental | Idarubicin Receives: Drug: Idarubicin |
| R1-DAUNO | Active comparator | Daunorubicin Receives: Drug: Daunorubicin |
| R2-HDAC | Active comparator | High dose cytarabine Receives: Drug: HD Cytarabine |
| R2-IDAC | Experimental | Intermediate dose cytarabine Receives: Drug: ID cytarabine |
| R3-MAC-MTX | Active comparator | Methotrexate and mycophenolic acid Receives: Drug: Methotrexate; Drug: Mycophenolic acid (MPA) |
| R3-MAC-MPA | Experimental | Cyclosporine and mycophenolic acid Receives: Drug: Cyclosporine; Drug: Mycophenolic acid (MPA) |
| R3-RIC-CICLO | Active comparator | Cyclosporine Receives: Drug: Cyclosporine |
| R3-RIC-MPA | Experimental | Cyclosporine and mycophenolic acid Receives: Drug: Cyclosporine; Drug: Mycophenolic acid (MPA) |
| R4-VOS-IDAC | Experimental | Intermediate dose cytarabine and vosaroxin Receives: Drug: vosaroxin; Drug: ID cytarabine |
| R4-IDAC (without VOS) | Active comparator | Intermediate dose cytarabine alone Receives: Drug: ID cytarabine |
| R4-DEX-HDAC | Experimental | High dose cytarabine and dexamethasone Receives: Drug: HD Cytarabine; Drug: Dexamethasone |
| R4-HDAC (without DEX) | Active comparator | High dose cytarabine alone Receives: Drug: HD Cytarabine |
| R4-VEN-IDAC | Experimental | Intermediate dose cytarabine and venetoclax Receives: Drug: ID cytarabine; Drug: Venetoclax |
| R4-IDAC (without VEN) | Active comparator | Intermediate dose cytarabine alone Receives: Drug: ID cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
For randomizations R1 (idarubicine vs daunorubicine) and R2 (HDAC vs IDAC)
Measured: 3 years
Cumulative incidence (CI) of acute Graft versus Host Disease (GvHD) of grade II to IV
For randomization R3 : GvHD prophylaxis study
Measured: 100 days
Disease free survival
For randomizations R4
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2015 (estimated)
- Study startJan 2015
- Primary completion30 Jul 2025
- Study completionJan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02416388
- Sponsor's protocol ID
- 49RC10_0046
- Acronym
- BIG-1
- Status last verified
- Jul 2026
- First submitted
- 7 Apr 2015
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Duployez N, Joudinaud R, Boudry A, Hunault M, Fenwarth L, Tavernier E, Pautas C, Bertoli S, Tavitian S, Raffoux E, Hospital MA, Marchand T, Heiblig M, Chantepie S, Carre M, Peterlin P, Gallego-Hernanz MP, Guieze R, Simand C, Turlure P, Huynh A, Lemasle E, Gabellier L, Lambert J, Suarez F, Chraibi S, Sanhes L, Celli-Lebras K, Mineur A, Gardin C, Ifrah N, Vey N, Peffault De Latour R, Rigolot L, Luquet I, Penther D, Itzykson R, Delabesse E, Hamel JF, De Botton S, Pigneux A, Dombret H, Recher C, Preudhomme C, Dumas PY. Prognostic impact of FLT3-ITD microclones in young adults with acute myeloid leukemia treated with intensive chemotherapy. Blood. 2026 Jul 30;148(5):598-609. doi: 10.1182/blood.2025032829.
PubMed 42166362Hunault M, Pautas C, Bertoli S, Dumas PY, Raffoux E, Hospital MA, Marchand T, Heiblig M, Chantepie S, Carre M, Peterlin P, Gallego-Hernanz MP, Lemasle E, Guieze R, Simand C, Turlure P, Huynh A, Leguay T, Devillier R, Quoc SN, Duployez N, Luquet I, Penther D, Celli-Lebras K, Mineur A, Raus N, Gardin C, Socie G, Cahn JY, Ifrah N, Vey N, de Latour RP, Delabesse E, Preudhomme C, Hamel JF, Pigneux A, Recher C, Dombret H. Intermediate-Dose Cytarabine as Postinduction AML Therapy. NEJM Evid. 2025 Jul;4(7):EVIDoa2400326. doi: 10.1056/EVIDoa2400326. Epub 2025 Jun 24.
PubMed 40552969
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II/III Randomized Study to Improve Overall Survival 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 Mycophenolate Mofetil Prophylaxis of Graft Versus Host Disease in Allografted Patients in First CR : a Backbone InterGroup-1 Trial
- ClinicalTrials.gov ID
- NCT02416388
- Acronym / sponsor ID
- BIG-1 / 49RC10_0046
- Conditions
- Acute Myeloid Leukemia (AML)
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 3,100 participants (estimated)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- Jan 2015
- Primary completion
- 30 Jul 2025 (actual)
- Study completion
- Jan 2032 (estimated)
- First posted
- 15 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| R1-IDA | Experimental | Drug: IdarubicinIdarubicin |
| R1-DAUNO | Active comparator | Drug: DaunorubicinDaunorubicin |
| R2-HDAC | Active comparator | Drug: HD CytarabineHigh dose cytarabine |
| R2-IDAC | Experimental | Drug: ID cytarabineIntermediate dose cytarabine |
| R3-MAC-MTX | Active comparator | Drug: Methotrexate, Drug: Mycophenolic acid (MPA)Methotrexate and mycophenolic acid |
| R3-MAC-MPA | Experimental | Drug: Cyclosporine, Drug: Mycophenolic acid (MPA)Cyclosporine and mycophenolic acid |
| R3-RIC-CICLO | Active comparator | Drug: CyclosporineCyclosporine |
| R3-RIC-MPA | Experimental | Drug: Cyclosporine, Drug: Mycophenolic acid (MPA)Cyclosporine and mycophenolic acid |
| R4-VOS-IDAC | Experimental | Drug: vosaroxin, Drug: ID cytarabineIntermediate dose cytarabine and vosaroxin |
| R4-IDAC (without VOS) | Active comparator | Drug: ID cytarabineIntermediate dose cytarabine alone |
| R4-DEX-HDAC | Experimental | Drug: HD Cytarabine, Drug: DexamethasoneHigh dose cytarabine and dexamethasone |
| R4-HDAC (without DEX) | Active comparator | Drug: HD CytarabineHigh dose cytarabine alone |
| R4-VEN-IDAC | Experimental | Drug: ID cytarabine, Drug: VenetoclaxIntermediate dose cytarabine and venetoclax |
| R4-IDAC (without VEN) | Active comparator | Drug: ID cytarabineIntermediate dose cytarabine alone |
Who may qualify
- Ages
- 18 to 61 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (58 listed)
- Age ≥ 18 years and < 61 years
- With a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome MDS or therapy-related AML)
- No prior treatment for neither AML (with the exception of hydroxyurea), nor MDS (with the exception of EPO)
- ECOG performance status ≤ 3
- Absence of severe uncontrolled infection
Key exclusion criteria (22 listed)
- 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)
- ------------------------------------------
- 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)
- ------------------------------------------
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IdarubicinInduction chemotherapy : Idarubicin 9mg/m² /day, from D1 to D5 (IV, 30min) + cytarabine 200mg/m²/day from D1 to D7 (IV 24 h) Bone marrow aspirate on D15 : if medullary blasts rate < 5% → G-CSF (5 μg/kg/day) until hematopoietic recovery (PNN ≥ 1 G/L). | Drug | R1-IDA |
| DaunorubicinInduction chemotherapy : Daunorubicin 90mg/m²/day, from D1 to D3 (IV, 30min) + cytarabine 200mg/m² /day from D1 to D7 (IV 24 h) Bone marrow aspirate on D15 : if medullary blasts rate < 5% → G-CSF (5 μg/kg/day) until hematopoietic recovery (PNN ≥ 1 G/L). | Drug | R1-DAUNO |
| HD CytarabineConsolidation chemotherapy course (s) : -High dose cytarabine: 3g/m² /12h on D1, D3 and D5 For all patients, G-CSF (5 μg/kg/day) : SC or IV (30 min) from D8 until hematopoietic recovery (PNN ≥ 1 G/L) Up to 3 consolidation courses, depending on the patient AML risk group | Drug | R2-HDAC, R4-DEX-HDAC, R4-HDAC (without DEX) |
| CyclosporineGvHD prophylaxis post allogeneic SCT : -Cyclosporine : 3 mg/kg /day from D-1 (IV) or 6 mg/kg/day from D-3 (PO). Not to be stopped before D100 | Drug | R3-MAC-MPA, R3-RIC-CICLO, R3-RIC-MPA |
| MethotrexateGvHD prophylaxis post allogeneic SCT : -15 mg/m² on D+1 then 10 mg/m² on D+3, D+6 and D+11 | Drug | R3-MAC-MTX |
| Mycophenolic acid (MPA)GvHD prophylaxis post allogeneic SCT : * 720 mg BID from D0 to D+28 for HLA-identical siblings * 720 mg BID from D0 to D+45 for 10/10 HLA allele-matched unrelated donors | Drug | R3-MAC-MPA, R3-MAC-MTX, R3-RIC-MPA |
| vosaroxinConsolidation chemotherapy course (s) : -70 mg/m² on D1 and D4 | Drug | R4-VOS-IDAC |
| ID cytarabineConsolidation chemotherapy course (s) : -Intermediate dose cytarabine: 1.5g/m² /12h on D1, D3 and D5 For all patients, G-CSF (5 μg/kg/day) : SC or IV (30 min) from D8 until hematopoietic recovery (PNN ≥ 1 G/L) Up to 3 consolidation courses, depending on the patient AML risk group | Drug | R2-IDAC, R4-IDAC (without VEN), R4-IDAC (without VOS), R4-VEN-IDAC, R4-VOS-IDAC |
| DexamethasoneConsolidation chemotherapy course (s) : -10 mg/12h on D1, D3 and D5 | Drug | R4-DEX-HDAC |
| VenetoclaxConsolidation chemotherapy course (s) : Once RP2D has been determined from the results of the dose selection phase (phase 1), the optimal dose level retained for randomized phase 2 will be one of the following: * 100 mg/d on D1 to D8 (selection phase dose level 1) * or 200 mg/d on D1 to D8 (selection phase dose level 2) * or 400 mg/d on D1 to D8 (selection phase dose level 3) * or 400 mg/d on D1 to D14 (selection phase dose level 4) | Drug | R4-VEN-IDAC |
Primary outcome
Overall survival
Time frame: 3 years
For randomizations R1 (idarubicine vs daunorubicine) and R2 (HDAC vs IDAC)
Cumulative incidence (CI) of acute Graft versus Host Disease (GvHD) of grade II to IV
Time frame: 100 days
For randomization R3 : GvHD prophylaxis study
Disease free survival
Time frame: 18 months
For randomizations R4
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2026.
- Derived from this study: PubMed 42166362Duployez N, Joudinaud R, Boudry A, Hunault M, Fenwarth L, Tavernier E, Pautas C, Bertoli S, Tavitian S, Raffoux E, Hospital MA, Marchand T, Heiblig M, Chantepie S, Carre M, Peterlin P, Gallego-Hernanz MP, Guieze R, Simand C, Turlure P, Huynh A, Lemasle E, Gabellier L, Lambert J, Suarez F, Chraibi S, Sanhes L, Celli-Lebras K, Mineur A, Gardin C, Ifrah N, Vey N, Peffault De Latour R, Rigolot L, Luquet I, Penther D, Itzykson R, Delabesse E, Hamel JF, De Botton S, Pigneux A, Dombret H, Recher C, Preudhomme C, Dumas PY. Prognostic impact of FLT3-ITD microclones in young adults with acute myeloid leukemia treated with intensive chemotherapy. Blood. 2026 Jul 30;148(5):598-609. doi: 10.1182/blood.2025032829.
- Derived from this study: PubMed 40552969Hunault M, Pautas C, Bertoli S, Dumas PY, Raffoux E, Hospital MA, Marchand T, Heiblig M, Chantepie S, Carre M, Peterlin P, Gallego-Hernanz MP, Lemasle E, Guieze R, Simand C, Turlure P, Huynh A, Leguay T, Devillier R, Quoc SN, Duployez N, Luquet I, Penther D, Celli-Lebras K, Mineur A, Raus N, Gardin C, Socie G, Cahn JY, Ifrah N, Vey N, de Latour RP, Delabesse E, Preudhomme C, Hamel JF, Pigneux A, Recher C, Dombret H. Intermediate-Dose Cytarabine as Postinduction AML Therapy. NEJM Evid. 2025 Jul;4(7):EVIDoa2400326. doi: 10.1056/EVIDoa2400326. Epub 2025 Jun 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mathilde Hunault, PD contact
56 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Idarubicin, Daunorubicin and HD Cytarabine in people with Acute Myeloid Leukemia (AML), run by University Hospital, Angers at 56 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 58 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 56 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mathilde Hunault, PD (MaHunault@chu-angers.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 3 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02416388, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2026.