Phase II, multicenter, randomized, open label trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus cytarabine and daunorubicin in patients with untreated AML 60-75 years of age.

ArticleinBlood · March 2014with14 Reads
Impact Factor: 10.45 · DOI: 10.1182/blood-2013-12-540971 · Source: PubMed

    Abstract

    CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this Phase II study newly diagnosed older AML patients were randomized 2:1 to first-line CPX-351 or 7+3 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (CR+CRi) was the primary endpoint, with event-free survival (EFS) and overall survival (OS) as secondary endpoints. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7%vs.51.2%, P=0.07), meeting predefined criteria for success (P<0.1). Differences in EFS and OS were not statistically significant. A planned analysis of the secondary AML subgroup demonstrated an improved response rate (57.6% vs.31.6%, P=0.06), and prolongation of EFS (HR=0.59, P=0.08) and OS (HR=0.46, P=0.01). Recovery from cytopenias was slower following CPX-351 (median days to ANC≥1000: 36vs.32; Platelets >100K: 37vs.28) with more grade 3-4 infections but without increase in infection-related deaths (3.5%vs.7.3%) or 60-day mortality (4.7% vs.14.6%) indicating acceptable safety. These results suggest clinical benefit with CPX-351, particularly among patients with secondary AML and provide the rationale for a Phase III trial currently underway in newly diagnosed secondary AML patients. This study was registered at Clinicaltrials.gov, identifier: NCT00788892.