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
In brief
Standard chemo gives 11% better two-year event-free survival than CPX-351
In a phase III trial of 721 children and young adults with newly diagnosed FLT3-wildtype AML, standard daunorubicin plus cytarabine induction achieved a 62% two-year event-free survival versus 51% with liposomal CPX-351, prompting early trial termination for futility. The advantage was driven by lower survival and higher relapse in low-risk patients, while high-risk outcomes were similar.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 24 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Jessica A Pollard, Todd A Alonzo, Robert B Gerbing, Matthew Kutny, Betsy Hirsch, Gordana Raca, et al.
- PMID
- 42497367
- DOI
- 10.1200/JCO-25-02979
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 27 July 2026): Phase III CPX‑351 vs standard induction in pediatric AML
- Picked for Transplantation (top studies of the week, 26 July 2026): High-quality evidence in a top journal
- Picked for Pediatrics and Child Health (paper of the day, 25 July 2026): Ranked by evidence level and journal quartile
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.