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

Sponsor
University Hospital, Angers
Study ID
NCT02416388
Phase
PHASE2/PHASE3
Status
Recruiting
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Conditions

  • Acute Myeloid Leukemia (AML)

Eligibility Criteria

Sex
ALL
Age
18 Years - 61 Years
Healthy Volunteers
Not accepted

Interventions

  • 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)

Study Details

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.

Key Dates

Start date
Jan 31, 2015
Status verified
Aug 2024
Primary completion
Jul 31, 2025
Completion
Jan 31, 2032

Study Design

Enrollment
3,100 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: R1-IDA
    Idarubicin
  • Active Comparator: R1-DAUNO
    Daunorubicin
  • Active Comparator: R2-HDAC
    High dose cytarabine
  • Experimental: R2-IDAC
    Intermediate dose cytarabine
  • Active Comparator: R3-MAC-MTX
    Methotrexate and mycophenolic acid
  • Experimental: R3-MAC-MPA
    Cyclosporine and mycophenolic acid
  • Active Comparator: R3-RIC-CICLO
    Cyclosporine
  • Experimental: R3-RIC-MPA
    Cyclosporine and mycophenolic acid
  • Experimental: R4-VOS-IDAC
    Intermediate dose cytarabine and vosaroxin
  • Active Comparator: R4-IDAC (without VOS)
    Intermediate dose cytarabine alone
  • Experimental: R4-DEX-HDAC
    High dose cytarabine and dexamethasone
  • Active Comparator: R4-HDAC (without DEX)
    High dose cytarabine alone
  • Experimental: R4-VEN-IDAC
    Intermediate dose cytarabine and venetoclax
  • Active Comparator: R4-IDAC (without VEN)
    Intermediate dose cytarabine alone

Primary Outcome Measure

Overall survival [ Time Frame: 3 years ]

Central Contacts

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