Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML

Sponsor
Children's Hospital of Soochow University
Study ID
NCT06221683
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
N/A - 18 Years
Healthy Volunteers
Not accepted

Interventions

  • Homoharringtonine — DRUG
    3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤10kg, d1-7, ivgtt, qd, more than 6 hours
  • Cytarabine — DRUG
    100mg/m2/q12h for weighing \>10kg, 3.3mg/kg/q12h for weighing ≤10kg, d1-7, ivgtt, q12h, more than 30 minutes in SDC group; 10mg/m2/q12h for weighing \>10kg, 0.33mg/kg/q12h for weighing ≤10kg, d1-10, s.c.,q12h (the first dose at 8 am) in the LDC group;
  • Etoposide — DRUG
    100mg/m2/d for weighing \>10kg, 3.3mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 4 hours
  • Venetoclax — DRUG
    100mg/m2/d for weighing \>10kg, 3.33mg/kg/d for weighing ≤10kg, d12-25, po, qd
  • Mitoxantrone hydrochloride liposome — DRUG
    5mg/m2/d for weighing \>10kg, 0.17mg/kg/d for weighing ≤ 10kg, d1, 3, 5, ivgtt, qod, more than 2 hours at 10 am.
  • Recombinant Human Granulocyte Colony-Stimulating Factor — DRUG
    5ug/kg/d, d1-10, s.c., qd, at 1pm
  • Idarubicin Hydrochloride — DRUG
    3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 6 hours.
  • Sorafenib — DRUG
    100mg/m2/day for weighing \>10kg, 3.3mg/kg/day for weighing ≤10kg, from identification, po, qd
  • Gilteritinib — DRUG
    20mg/m2/day for weighing \>10kg, 0.7mg/kg/day for weighing ≤ 10kg, from identification, po, qd
  • Avapritinib — DRUG
    50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd

Study Details

The goal of this clinical trial is to estimate the rate (probability) of complete remission or complete remission with incomplete count recovery (CR/CRi) with negative MRD after induction I and II, event-free survival (EFS), and cumulative incidence (probability) of relapse (CIR), in patients receiving molecular/precision medicine and MRD-driven remission inductions, and to assess secondarily if there is an improvement over the AML2018 protocol.

Key Dates

Start date
Jan 1, 2024
Status verified
Aug 2024
Primary completion
Dec 31, 2028
Completion
Dec 31, 2029

Study Design

Enrollment
500 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT

Arms

  • Experimental: SDC group
    Patients with CBF fusion gene (RUNX1: : RUNX1T1 and CBFB: : MYH11) or KMT2A: : MLLT3(AF9) , KMT2A: : MLLT10(AF10) , KMT2A: : MLLT4(AF6) fusion gene or KIT mutation will receive SDC regimen, including one course of HAE (Homoharringtonine, cytarabine, etoposide) in induction I. These patients will continue on the SDC (HAE) regimen in the second course if the MRD is \< 1% after induction I, otherwise venetoclax will be added to the SDC group sequentially on Day 2 after the end of HAE. FLT3-ITD will be given sorafenib or gilteritinib as early as possible, and patients with KIT mutations will be recommended to add avapritinib as appropriate. These targeted drugs will not be combined with venetoclax.
  • Experimental: LDC group
    Patients with the exception of the CBF fusion gene (RUNX1: : RUNX1T1 and CBFB: : MYH11) or those with the KMT2A: : MLLT3(AF9) , KMT2A: : MLLT10(AF10) , KMT2A: : MLLT4(AF6) fusion gene or KIT mutation will receive the LDC (MAG/IDAG+ venetoclax) regimen in induction I. Patients with MRD ≥1% or KIT mutations, assessed after induction I, will receive the HAE plus venetoclax (or targeted drugs) regimen, otherwise, they will receive MAG/IDAG + venetoclax. FLT3-ITD will be given sorafenib or gilteritinib as early as possible, and patients with KIT mutations will be recommended to add avapritinib as appropriate. These targeted drugs will not be combined with venetoclax.

Primary Outcome Measure

Rate of CR/CRi with negative MRD [ Time Frame: Day 26 (HAE group) and Day 32 (MAG+Ven group) for remission induction 1 and 2 are the necessary time points for response evaluation. ]

Central Contacts

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