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

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.

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/m² daunorubicin/dose or 59 mg/m² 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.

The RP2D was determined to be 44 mg/m² 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.

CPX-351 at 44 mg/m² 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.