The CHIP-AML22 Master protocol has the overall aim of increasing the cure rate in newly diagnosed pediatric de novo AML patients, while avoiding unnecessary toxicity.
Newly diagnosed AML as defined by the diagnostic criteria in section 8.1. Note that different blast thresholds may apply for different genetic abnormalities in case of low blast percentages. The origin of AML must be de novo (not secondary to bone marrow failure or therapy-related).
Age ≥ day and ≤18 years old at initial diagnosis.
Written informed consent/assent from patients and/or from parents or legal guardians for minor patients, according to local law and regulations. Informed consent should ideally be obtained before day 7 of induction course 1, as patients that are eligible for the linked quizartinib trial should be enrolled before the end of induction course 1, and in view of the planned Mylotarg® randomisation. Thus, standard of care diagnostics and induction treatment may be started before informed consent has been obtained.
Able to comply with scheduled follow-up and with management of toxicity.
Previous chemotherapy or radiotherapy. This includes patients with therapy-related AML after previous cancer therapy. These patients may be treated according to the master protocol but will not be part of the formal study population, and data of these patients will not be collected.
Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia.
Myeloid Leukemia of Down syndrome (ML-DS). Patients with ML-DS are recommended to be treated according to the international ML-DS protocol. Patients with AML and DS older than 5 years who often lack GATA1 mutation and do not have typical myeloid leukemia of DS may be treated according to the master protocol but will not be part of the formal study population, hence data of these patients will not be collected.
Acute promyelocytic leukemia (APL).
Parallel
Standard Intervention Rc
Drug3 consolidation courses (HAM + HA3E + FLA)
Investigational Intervention Rc
Drug2 consolidation courses (HAM + FLA)
Standard Intervention Ri
DrugNo addition of GO to first induction course
Investigational Intervention Ri
DrugAddition of GO to first induction course
Overarching primary objective
Event Free Survival (EFS)
Primary objective Randomisation Consolidation
Disease Free Survival (DFS)
Primary objective Randomisation Induction
MRD \<0.1% leukemic cells in the BM
Overarching secondary objective - efficacy 1
• Bone marrow blast counts by morphology and multicolor flow cytometry (MFCM) after course #1 and #2 and before allo-SCT
Overarching secondary objective - efficacy 2
ORR (CR, CRp, and CRi) and morphologic leukemia-free state (MLFS) rates after course #1 and #2;
Overarching secondary objective - efficacy 3
MRD negativity after course #1 and #2 and before allo-SCT
Overarching secondary objective - efficacy 4
Absolute MRD levels after course #1 and #2 and before allo-SCT
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Princess Maxima Center for Pediatric Oncology
Lead sponsor
European Commission
Collaborator
