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CPX‐351 in High‐Risk Relapsed Pediatric Acute Leukemia: Real‐World Phase 1 Data Establishing the FDA‐Approved Dose

Year: 2026

Type: article

Abstract: ABSTRACT Background/Objectives Outcomes for pediatric relapsed/refractory (R/R) acute myeloid leukemia (AML) remain dismal. CPX‐351, a liposomal formulation of cytarabine and daunorubicin, may have less off‐target toxicities than traditional chemotherapies and has shown improved outcomes for adults with newly diagnosed therapy‐related AML. Design/Methods In this first‐in‐pediatric, single center phase 1 study (NCT01943682), 27 patients with R/R acute leukemia (acute lymphoblastic leukemia [ALL, n = 3], AML [ n = 23], or mixed phenotype acute leukemia [MPAL, n = 1]) received one cycle of CPX‐351 (on days 1, 3, 5) at either 44 mg/m 2 daunorubicin/dose or 59 mg/m 2 daunorubicin/dose. The primary objectives were to determine the CPX‐351 recommended phase 2 dose (RP2D) and to evaluate its tolerability; secondary objectives were to assess marrow overall response rate (ORR) and cardiotoxicity. Results The RP2D was determined to be 44 mg/m 2 daunorubicin/dose. Grade ≥3 non‐hematologic toxicities occurred in 89% of patients including febrile neutropenia (85%), infection (52%), and maculo‐papular rash (37%). No grade ≥3 acute cardiac toxicities or significant changes in cardiac biomarkers were detected. The marrow ORR for AML patients was 48% (10/21 evaluable patients), despite high‐risk genetic findings in most and nearly half of patients having undergone prior hematopoietic stem cell transplant. No patients with ALL or MPAL responded. Conclusion CPX‐351 at 44 mg/m 2 daunorubicin/dose was safe and tolerable in children with R/R acute leukemia, showing promising activity in heavily pretreated, high‐risk AML and is now the FDA‐approved pediatric dose for therapy‐related AML or AML with myelodysplastic changes.

Source: Pediatric Blood & Cancer

DOI: 10.1002/1545-5017.70268