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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

ConditionAcute Myeloid Leukemia (AML)
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18-61
SponsorUniversity Hospital, Angers

About this 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Idarubicin

    Drug

    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).

  • Daunorubicin

    Drug

    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 Cytarabine

    Drug

    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

  • Cyclosporine

    Drug

    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

  • Methotrexate

    Drug

    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

  • vosaroxin

    Drug

    Consolidation chemotherapy course (s) : -70 mg/m² on D1 and D4

  • ID cytarabine

    Drug

    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

  • Dexamethasone

    Drug

    Consolidation chemotherapy course (s) : -10 mg/12h on D1, D3 and D5

  • Venetoclax

    Drug

    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)

Treatment groups

3,100 Participants
are divided into 14 treatment groups

14

Treatment groups

See each treatment group below.

Group A: R1-IDAExperimental treatment 1 intervention
Group B: R1-DAUNOActive comparator 1 intervention
Group C: R2-HDACActive comparator 1 intervention
Group D: R2-IDACExperimental treatment 1 intervention
Group E: R3-MAC-MTXActive comparator 2 interventions
Group F: R3-MAC-MPAExperimental treatment 2 interventions
Group G: R3-RIC-CICLOActive comparator 1 intervention
Group H: R3-RIC-MPAExperimental treatment 2 interventions
Group I: R4-VOS-IDACExperimental treatment 2 interventions
Group J: R4-IDAC (without VOS)Active comparator 1 intervention
Group K: R4-DEX-HDACExperimental treatment 2 interventions
Group L: R4-HDAC (without DEX)Active comparator 1 intervention
Group M: R4-VEN-IDACExperimental treatment 2 interventions
Group N: R4-IDAC (without VEN)Active comparator 1 intervention

Trial outcomes

Primary outcomes

1

Overall survival

For randomizations R1 (idarubicine vs daunorubicine) and R2 (HDAC vs IDAC)

Time frame
3 years
2

Cumulative incidence (CI) of acute Graft versus Host Disease (GvHD) of grade II to IV

For randomization R3 : GvHD prophylaxis study

Time frame
100 days
3

Disease free survival

For randomizations R4

Time frame
18 months

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Hospital, Angers

Lead sponsor

Source ClinicalTrials.gov
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