AAML1831: A Phase III Trial Comparing Standard Induction Therapy With CPX-351 in De Novo Pediatric AML: A Report From the Children's Oncology Group

PURPOSE The Children's Oncology Group phase III clinical trial AAML1831 (ClinicalTrials.gov identifier: NCT04293562 ) evaluated liposomal daunorubicin and cytarabine (CPX-351) versus standard daunorubicin/cytarabine (DA) induction therapy in children and young adults with newly diagnosed AML. We hypothesized that CPX-351 given during induction 1 and 2 would improve outcomes compared with DA. PATIENTS AND METHODS Patients (21 years and younger) were randomly assigned to two cycles of DA induction (arm A = DA) or CPX-351 (arm B = CPX-351). All patients also received gemtuzumab ozogamicin in induction 1. Postinduction chemotherapy was according to risk assignment made at the end of induction 1 (EOI1). Those with high-risk (HR) AML received consolidation with allogeneic hematopoietic stem-cell transplantation (HSCT), whereas low-risk (LR) patients received chemotherapy alone. Protocol-specified interim analysis monitored efficacy and futility of CPX-351 induction with respect to the primary end point, event-free survival (EFS) from study entry. Disease-free survival (DFS) was calculated to determine the impact of EOI1 risk assignment. RESULTS Seven hundred twenty-one eligible patients with FLT3 wild-type AML were randomly assigned to DA (n = 358) or CPX-351 (n = 363). Interim analysis determined that the futility monitoring rule was crossed because of inferior EFS in the CPX-351 arm and the random assignment was stopped. The two-year EFS from study entry was 62.2% for DA versus 51.2% for CPX-351 ( P = .011). DFS for patients with HR AML was comparable for both arms. However, DFS was significantly lower and cumulative incidence of relapse (CIR) was higher for LR patients assigned to CPX-351 versus DA (2-year DFS from EOI1: DA: 73.8% v CPX-351 57.5% [ P = .001]; 2-year CIR Arm DA: 23.6% v CPX-351: 39.9% [ P = .001]). CONCLUSION CPX-351 was inferior to DA induction in the AAML1831 trial with differential EFS largely driven by events in LR patients.

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Journal
Journal of Clinical Oncology
Published
2026-07-24
DOI
https://doi.org/10.1200/jco-25-02979
Primary Topic
Acute Myeloid Leukemia Research
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article
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article

AAML1831: A Phase III Trial Comparing Standard Induction Therapy With CPX-351 in De Novo Pediatric AML: A Report From the Children's Oncology Group

E. Anders Kolb, Aman Wadhwa, Richard Aplenc, Todd M. Cooper et al.
Journal of Clinical Oncology
Acute Myeloid Leukemia Research
article

AAML1831: A Phase III Trial Comparing Standard Induction Therapy With CPX-351 in De Novo Pediatric AML: A Report From the Children's Oncology Group

E. Anders Kolb, Aman Wadhwa, Richard Aplenc, Todd M. Cooper, Jennifer Jill Wilkes, Karen M. Chisholm, Olga Militano, Samir B. Kahwash, Betsy Hirsch, Andrew J. Menssen, Michael R. Loken, Sarah K. Tasian, Jessica A. Pollard, Zachary Graff, Reena Pabari, Katherine Tarlock, Lisa Eidenschink Brodersen, Kasey J. Leger, Bonnie Ky, Sarah Menig, Chad Hudson, Matthew Kutny, John Horan, Robert B. Gerbing, Todd A. Alonzo, Andrew Place, Soheil Meshinchi, Joseph Chewning, Gordana Raca
article en

Abstract

PURPOSE The Children's Oncology Group phase III clinical trial AAML1831 (ClinicalTrials.gov identifier: NCT04293562 ) evaluated liposomal daunorubicin and cytarabine (CPX-351) versus standard daunorubicin/cytarabine (DA) induction therapy in children and young adults with newly diagnosed AML. We hypothesized that CPX-351 given during induction 1 and 2 would improve outcomes compared with DA. PATIENTS AND METHODS Patients (21 years and younger) were randomly assigned to two cycles of DA induction (arm A = DA) or CPX-351 (arm B = CPX-351). All patients also received gemtuzumab ozogamicin in induction 1. Postinduction chemotherapy was according to risk assignment made at the end of induction 1 (EOI1). Those with high-risk (HR) AML received consolidation with allogeneic hematopoietic stem-cell transplantation (HSCT), whereas low-risk (LR) patients received chemotherapy alone. Protocol-specified interim analysis monitored efficacy and futility of CPX-351 induction with respect to the primary end point, event-free survival (EFS) from study entry. Disease-free survival (DFS) was calculated to determine the impact of EOI1 risk assignment. RESULTS Seven hundred twenty-one eligible patients with FLT3 wild-type AML were randomly assigned to DA (n = 358) or CPX-351 (n = 363). Interim analysis determined that the futility monitoring rule was crossed because of inferior EFS in the CPX-351 arm and the random assignment was stopped. The two-year EFS from study entry was 62.2% for DA versus 51.2% for CPX-351 ( P = .011). DFS for patients with HR AML was comparable for both arms. However, DFS was significantly lower and cumulative incidence of relapse (CIR) was higher for LR patients assigned to CPX-351 versus DA (2-year DFS from EOI1: DA: 73.8% v CPX-351 57.5% [ P = .001]; 2-year CIR Arm DA: 23.6% v CPX-351: 39.9% [ P = .001]). CONCLUSION CPX-351 was inferior to DA induction in the AAML1831 trial with differential EFS largely driven by events in LR patients.

Journal of Clinical Oncology
University of Southern California (US), University of Minnesota (US), Nationwide Children's Hospital (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Children's Hospital of Philadelphia (US), Children's Hospital of Los Angeles (US), University of Toronto (CA), University of Washington (US), Medical College of Wisconsin (US), Hospital for Sick Children (CA), University of Rochester Medical Center (US), University of Alabama at Birmingham (US), Fred Hutch Cancer Center (US), White Plains Hospital (US), Arcadia (US), Seattle Children's Hospital (US), Children's Oncology Group (US), SickKids Foundation (CA), Dana-Farber/Boston Children's Cancer and Blood Disorders Center (US), The Ohio State University (US), University of Pennsylvania (US)
Good health and well-being
Openalex Percentile: Top 9%
Acute Myeloid Leukemia Research
DOISourceOpenAlex
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