CPX-351 appears to be promising for treating relapsed acute myeloid leukemia (AML) in pediatric patients, according to a phase 2 trial published in the Journal of Clinical Oncology.

While standard treatments can be effective in pediatric AML, long-term toxicity, particularly anthracycline-induced cardiomyopathy, remains a significant issue in this patient population. Therefore, new therapies for reducing cardiotoxicity are needed.

CPX-351, a liposomal preparation of daunorubicin and cytarabine, received approval from the US Food and Drug Administration in 2017 for a subset of adult patients with AML. AAML1421, a Children’s Oncology Group (COG)-sponsored phase 1/2 trial (ClinicalTrials.gov Identifier: NCT02642965), evaluated the safety and efficacy of CPX-351 in pediatric patients with relapsed AML. Primary objectives included response rate and determining the recommended phase 2 dose (RP2D).

Continue Reading

Overall, 38 patients (median age, 11.9 years) were included in the trial. Six patients were in the dose-finding phase and 32 patients were in the efficacy phase; 10 (26.3%) patients had undergone previous hematopoietic stem cell transplantation (HSCT). Patients were eligible to receive 2 cycles of therapy, with CPX-351 in cycle 1 and fludarabine, cytarabine, and granulocyte-colony stimulating factor (FLAG) in cycle 2.

The researchers determined the RP2D to be 135 units/m2 on days 1, 3, and 5. No toxicity-related mortalities were reported, though grade 3 or worse adverse events in the first treatment cycle included neutropenia (45%), infection (47%), and rash (40%).

Related Articles

There were 30 responses; 20 (54%) complete responses (CRs), 5 (14%) CRs with partial recovery of platelet count (CRp), and 5 (14%) CRs with incomplete blood count recovery. Of the 25 patients with CR/CRp, 21 (84%) had no detectible residual disease by flow cytometry. Consolidation HSCT was used in 29 (96.7%) patients who responded.

“These results support the efficacy of CPX-351 for children with AML in first relapse and provide excellent rationale for phase III study in childhood de novo AML,” the authors wrote.


Cooper TM, Absalon MJ, Alonzo TA, et al. Phase I/II study of CPX-351 followed by fludarabine, cytarabine, and granulocyte-colony stimulating factor for children with relapsed acute myeloid leukemia: a report from the Children’s Oncology Group [published online May 13, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.03306