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A multicenter phase II study of risk-stratified chemotherapy with azacitidine for children with ML-DS

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Myeloid leukemia with Down syndrome
Date of first enrollment	30/06/2025
Target sample size	145
Countries of recruitment
Study type	Interventional
Intervention(s)	Based on the age at diagnosis, the initial induction therapy is administered as follows; Patients under 2 years of age: cytarabine, etoposide and pirarubicin (CET) Patients aged 2 years and older: azacitidine and CET (AZA-CET) <Risk stratification> After the initial induction therapy, patients are stratified into risk groups based on the age at diagnosis, GATA1 mutation status, morphological treatment response, and flow cytometry minimal residual disease (FCM-MRD). Low-risk (LR) group: Patients under 2 years of age with hematological complete remission (CR) and negative FCM-MRD after the initial induction therapy, and positive GATA1 mutation Standard-risk (SR) group: (Patients under 2 years of age) hematological CR and negative FCM-MRD after the initial induction therapy, and negative GATA1 mutation (Patients aged 2 years and older) hematological CR and negative FCM-MRD after the initialinduction therapy MRD high-risk (MHR): Hematological CR and positive FCM-MRD after the initial induction therapy High-risk (HR) group: Hematological non-CR after the initial induction therapy <Post initial induction therapy> (1) LR Intensification L-1 (CET) -> Intensification L-2 (CT) -> Intensification L-3 (CT). (2) SR Intensification S-1 (AZA-CET) -> Intensification S-2 (AZA-CT) -> Intensification S-3 (AZA-CET) -> Intensification S-4 (AZA-CT). (3) MHR Intensification L-1 or S-1 (CET or AZA-CET) -> Intensification MH-2 (AZA-hCE) -> Intensification MH-3 (AZA-cCVT) -> Intensification MH-4 (AZA-hCE) -> Intensification MH-5 (AZA-cCVT). (4) HR Induction 2 (AZA-cCVT) -> Induction 3 (AZA-hCE) -> Intensification H-1 (AZA-cCVT) -> Intensification H-2 (AZA-hCE) -> Intensification H-3 (AZA-cCVT).

Outcome(s)

Primary Outcome

3-year event-free survival (EFS) in the non-LR group

Secondary Outcome

3-year overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) in the non-LR group 3-year OS, EFS, CIR, and NRM in the entire cohort 3-year OS, EFS, CIR, and NRM in each risk group Remission rate and positive rate of FCM-MRD in the entire cohort after the initial induction therapy Remission rate and positive rate of FCM-MRD in patients aged 2 years and older after the initial induction therapy Remission rate and positive rate of FCM-MRD in patients under 2 years of age after the initial induction therapy Positive rate of FCM-MRD after intensification therapy 1 and 2, and at the end of therapy in the MRD-HR group Remission rate after induction therapy 2 and 3, and positive rate of FCM-MRD after the initial induction therapy, induction therapy 2, induction therapy 3, and at the end of therapy in the HR group Incidence of myelosuppression, adverse events, treatment reductions, and deaths during the initial induction therapy in patients under 2 years of age, and in patients aged 2 years and older Incidence of myelosuppression, adverse events, delay in starting the subsequent treatment course, and treatment reductions during each treatment course in each risk group

Key inclusion & exclusion criteria

Age minimum	>= 4month old
Age maximum	< 18age old
Gender	Both
Include criteria	(1) Newly diagnosed myeloid leukemia with Down syndrome (ML-DS) including mosaicism DS (2) Age 4 months to <18 years at diagnosis (3) Patients who registered JPLSG-CHM-14 and have JPLSG number (4) Written informed consent from patient and guardian, or guardian
Exclude criteria	(1) Severe intracranial hemorrhage (grade 3 or more of CTCAE version 5.0) (2) Uncontrolled diabetes (3) Intractable heart failure (presence of congenital heart disease itself is not a exclusion criteria) (4) Uncontrolled infection (5) Pregnant or possibility of pregnancy (6) History of congenital or acquired immunodeficiencies (7) Central nervous system (CNS) leukemia (diagnostic lumbar puncture is performed only in case strongly suspected of CNS infiltration) (8) Acute promyelocytic leukemia (9) BCR::ABL1 positive AML (10) Acute leukemias of ambiguous lineage including mixed phenotype acute leukemia (11) Myeloid sarcoma (12) History of previous chemotherapy (except for chemotherapy for transient myeloproliferative disorder) or radiation therapy (13) Any inappropriate status judged by the primary investigators and co-investigators