A Multi-Center Seamless Phase II-III Randomized Trial of High-dose Cytarabine in Initial Induction with Evaluation of Flow-cytometry-based Minimal Residual Disease for Children with de Novo Acute Myeloid Leukemia (AML-12)

A Multi-Center Seamless Phase II-III Randomized Trial of High-dose Cytarabine in Initial Induction with Evaluation of Flow-cytometry-based Minimal Residual Disease for Children with de Novo Acute Myeloid Leukemia (AML-12) - AML-12

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

JPRN

Registry ID

JPRN-UMIN000013288

Enrollment

300

Registered

2014-03-01

Start date

2014-03-01

Completion date

Unknown

Last updated

2026-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Myeloid Leukemia

Interventions

&lt

Standard Arm&gt

Induction-1A (ECM): In the Phase II study, patients in the &quot

selected&quot

institutions will be randomly assigned to either high-dose cytarabine (Ara-C) induction (HD-ECM) or standard-dose Ara-C induction (ECM). Patients in the &quot

other&quot

institutions will be non-randomly assigned to the ECM induction. In Phase III study, all the patients will be randomly assigned to either HD-ECM or ECM. Standard arm &quot

Induction-1A (ECM)&quot

consists of standard dose Ara-C, mitoxantrone (MIT), etoposide (VP-16), and triple intrathecal therapy [TIT

Ara-C, methotrexate (MTX), and hydrocortisone (HDC)]. Induction-2 (HCEI): All the patients will receive HCEI consisted of high-dose Ara-C, VP-16, idarubicin (IDA), and TIT. Post-remission therap

Experimental Arm&gt

Induction-1B (HD-ECM): In the Phase II study, patients in the &quot

institutions will be non-randomly assigned to the ECM induction. In Phase III study, all the patients will be randomly assigned to either HD-ECM or ECM. Experimental arm &quot

Induction-1B (HD-ECM)&quot

consists of high-dose Ara-C, mitoxantrone (MIT), etoposide (VP-16), and triple intrathecal therap

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1) AML [excluding APL, AML with Down syndrome (ML-DS), secondary AML, AML developed after MDS, NK/myeloid leukemia, and granulocytic sarcoma] 2) Age 0 year to 18 years old at diagnosis; for neonates aged 30 days or less, patients must be >= 36 weeks gestational age at the time of diagnosis 3) ECOG performance status (PS) score of 0-2; those with PS score 3 is eligible if that is derived from AML 4) newly diagnosed AML without history of previous chemotherapy or radiation therapy; those with history of steroid therapy, ATRA (because of suspicion of APL), or single intrathecal methotrexate therapy (because of suspicion of ALL) are eligible 5) Patients must have sufficient organ function satisfying the laboratory data listed below (should be evaluated within 7 days of study enrollment); T-Bil: within 3x of the age-dependent normal range Cre: within 3x of the age-dependent normal range 6) All patients and/or their parents or legal guardians must sign a written informed consent.

Exclusion criteria

Exclusion criteria: 1) Patients with severe CNS hemorrhage (grade 3 or higher in CTCAE ver4.0) 2) Patients with uncontrollable infection (including those with active tuberculosis or positive HIV antibody) 3) Patients who are pregnant or breast-feeding mother 4) Patients with history of primary or acquired immunodeficiency 5) Patients with uncontrollable heart failure; presence of heart anomaly itself is not an exclusion criteria 6) Patients with any other inappropriate status judged by physician

Design outcomes

Primary

Measure	Time frame
<Phase II study> Early death rate <Phase III study> 1) 3-year event-free survival (EFS) rate 2) Positive rate of flow-cytometry-based minimal residual disease (FCM-MRD) after initial induction course (TP-1)	—

Secondary

Measure	Time frame
1) Overall response (CR+CRi) rate, CR rate, CRi rate, non-CR rate, early death rate, and bone marrow response after Induction-1 2) Rate of severe adverse events (grade 3 or higher) defined by Common Terminology Criteria for Adverse Events (CTCAE) ver4.0 3) Positive rate of FCM-MRD in TP-2 and TP-3 4) 3-year and 5-year EFS and overall survival (OS) rate 5) Relapse rate, non-relapse mortality 6) Comparison of FCM-MRD and MRD measuring WT1 mRNA expression 7) Subgroup analyses on all the endpoints; for the whole study cohort including "other" institutions in the Phase II study (except endpoints regarding MRD analyses) and according to the risk groups, MRD levels on TP-1 and TP-2, and other prognostic factors [age and WBC at diagnosis, WHO classification (ver4.0), cytogenetics (all the risk-stratifying factors, complex karyotype, FLT3-ITD allelic ratio, 11q23/MLL gene abnormalities, CEBPA mutation, NPM1 mutation, KIT mutation, and others] 8) For the high risk (HR) group, 3-year and 5-year post-transplantation EFS and OS for those transplanted in first remission (including subgroup analyses according to the donor type and conditioning regimen received)	—

Measure

Time frame

1) Overall response (CR+CRi) rate, CR rate, CRi rate, non-CR rate, early death rate, and bone marrow response after Induction-1 2) Rate of severe adverse events (grade 3 or higher) defined by Common Terminology Criteria for Adverse Events (CTCAE) ver4.0 3) Positive rate of FCM-MRD in TP-2 and TP-3 4) 3-year and 5-year EFS and overall survival (OS) rate 5) Relapse rate, non-relapse mortality 6) Comparison of FCM-MRD and MRD measuring WT1 mRNA expression 7) Subgroup analyses on all the endpoints; for the whole study cohort including "other" institutions in the Phase II study (except endpoints regarding MRD analyses) and according to the risk groups, MRD levels on TP-1 and TP-2, and other prognostic factors [age and WBC at diagnosis, WHO classification (ver4.0), cytogenetics (all the risk-stratifying factors, complex karyotype, FLT3-ITD allelic ratio, 11q23/MLL gene abnormalities, CEBPA mutation, NPM1 mutation, KIT mutation, and others] 8) For the high risk (HR) group, 3-year and 5-year post-transplantation EFS and OS for those transplanted in first remission (including subgroup analyses according to the donor type and conditioning regimen received)

—

Countries

Japan

Contacts

Public ContactDaisuke Tomizawa

National Center for Child Health and Development Division of Leukemia and Lymphoma, Children's Cancer Center

tomizawa-d@ncchd.go.jp03-3416-0181

Outcome results

None listed

Source: JPRN (via WHO ICTRP) · Data processed: Jul 3, 2026