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

Area of Science:

• Pediatric Oncology
• Hematology
• Pharmacology

Background:

• Outcomes for pediatric relapsed/refractory (R/R) acute myeloid leukemia (AML) are poor.
• CPX-351, a liposomal formulation of cytarabine and daunorubicin, may offer reduced toxicity compared to traditional chemotherapy.
• CPX-351 has demonstrated improved outcomes in adults with newly diagnosed therapy-related AML.

Purpose of the Study:

• Determine the recommended phase 2 dose (RP2D) of CPX-351 in pediatric patients with R/R acute leukemia.
• Evaluate the tolerability and safety of CPX-351 in this population.
• Assess the marrow overall response rate (ORR) and cardiotoxicity associated with CPX-351 treatment.

Main Methods:

• A single-center, first-in-pediatric phase 1 study (NCT01943682) enrolled 27 patients with R/R acute leukemia.
• Patients received one cycle of CPX-351 at either 44 mg/m² or 59 mg/m² daunorubicin/dose.
• Primary objectives included determining the RP2D and evaluating tolerability; secondary objectives focused on ORR and cardiotoxicity.

Main Results:

• The RP2D was established at 44 mg/m² daunorubicin/dose.
• Grade ≥3 non-hematologic toxicities were observed in 89% of patients, including febrile neutropenia (85%) and infections (52%).
• No grade ≥3 acute cardiac toxicities were detected. The marrow ORR for AML patients was 48% (10/21), with no responses in ALL or MPAL patients.

Conclusions:

• CPX-351 at 44 mg/m² daunorubicin/dose is safe and tolerable for pediatric R/R acute leukemia.
• The treatment demonstrated promising activity in heavily pretreated, high-risk AML.
• This dose is now the FDA-approved pediatric dose for therapy-related AML or AML with myelodysplastic changes.