AML-12

JRCT ID: jRCTs041180128

Registered date:26/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Acute Myeloid Leukemia
• Date of first enrollment: 04/04/2014
• Target sample size: 300
• Study type: Interventional

Intervention(s)

<Standard Arm>
Induction-1A (ECM): In the Phase II study, patients in the "selected" 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 "other" 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 "Induction-1A (ECM)" 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 therapies: All the patients who achieved CR after 2 course of induction chemotherapy (Induction-1 and Induction-2) will be stratified to either of the three risk groups (SR/CBF, SR/non-CBF, or HR) and undergo risk stratified multiple chemotherapy courses with or without hematopoietic stem cell transplantation (HSCT) in first remission. HSCT is indicated only for the HR group. Chemotherapy is consisted of Ara-C, MIT or IDA, VP-16, and TIT.
<Experimental Arm>
Induction-1B (HD-ECM): In the Phase II study, patients in the "selected" 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 "other" 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 "Induction-1B (HD-ECM)" consists of high-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 therapies: All the patients who achieved CR after 2 course of induction chemotherapy (Induction-1 and Induction-2) will be stratified to either of the three risk groups (SR/CBF, SR/non-CBF, or HR) and undergo risk stratified multiple chemotherapy courses with or without hematopoietic stem cell transplantation (HSCT) in first remission. HSCT is indicated only for the HR group. Chemotherapy is consisted of Ara-C, MIT or IDA, VP-16, and TIT.

Outcome(s)

Primary Outcome

<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 Outcome

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)

Key inclusion & exclusion criteria

• Age minimum: >=
• Age maximum: < 18age old
• Gender: Both

Include 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.

Exclude 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

Related Information

• Primary Sponsor: Adachi Souichi
• Source(s) of Monetary Support: Ministry of Health, Labour and Welfare,National Center for Child Health and Development
• Secondary ID(s): UMIN000013288