An Open Label Complex Clinical Trial in Newly Diagnosed Pediatric de Novo AML Patients - a Study by the NOPHO-DB-SHIP Consortium, Master Protocol

2023-504999-25-00

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.

2023-07-14

2031-03-01

2035-12-01

Recruiting

Early phase I

905

General inclusion criteria for CHIP-AML22/Master: Patients are eligible for the study if they fulfil all four criteria below: 1. 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). 2. Age ≥ day and ≤18 years old at initial diagnosis. 3. 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. 4. Able to comply with scheduled follow-up and with management of toxicity. Additional inclusion criteria for Ri randomization 1. CD33 positivity of leukemic blasts as measured by flow cytometry at diagnosis (bone marrow aspirate and/or peripheral blood). 2. Informed consent for participation in randomization Ri Additional inclusion criteria for Rc randomization 1. Patients included in the CHIP-AML22 protocol and stratified to Standard Risk Group according to the stratification algorithm of the protocol 2. Informed consent for participation in randomization Rc General exclusion criteria for CHIP-AML22/Master Patients are excluded if any of the criteria below are present: 1. 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. 2. Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia. 3. 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. 4. Acute promyelocytic leukemia (APL). 5. Myelodysplastic syndrome (MDS). 6. Juvenile Myelomonocytic Leukemia (JMML). 7. Known intolerance to any of the chemotherapeutic drugs in the protocol. 8. Evidence of cardiac dysfunction (shortening fraction below 28%). 9. Pregnant or lactating patients, or sexually active female patients of childbearing potential not willing to use an highly effective method of contraception for the duration of study therapy and up to 7 months after the completion of all study therapy. 10. Sexually active, fertile male patients, not willing to use an effective method of contraception, for the duration of study therapy, and up to 6 months after the completion of all study therapy. 11. Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in this protocol or in one of the trials linked to this Master protocol, is not allowed. 12. Patients who in the opinion of the investigator, may not be able to comply with the study requirements of the study. 13. Patients with known active hepatitis B, hepatitis C, or HIV infection. 14. Patients for whom informed consent was not obtained.

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2024-02-14