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

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. 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)

Interventions

DRUG

Idarubicin

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).

DRUG

Daunorubicin

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).

DRUG

HD Cytarabine

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

DRUG

Cyclosporine

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

DRUG

Methotrexate

GvHD prophylaxis post allogeneic SCT : -15 mg/m² on D+1 then 10 mg/m² on D+3, D+6 and D+11

DRUG

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

vosaroxin

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

DRUG

ID cytarabine

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

DRUG

Dexamethasone

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

DRUG

Venetoclax

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)

Sponsors & Collaborators

• University Hospital, Angers

  lead OTHER_GOV

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

61 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-01-31

Primary Completion

2025-07-31

Completion

2032-01-31

Countries

• France

Study Locations