On May 27, 2014 Celator Pharmaceuticals reported the publication of the Phase 2 study evaluating CPX-351 in newly diagnosed older patients with acute myeloid leukemia (AML) in Blood, the official journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release Celator Pharmaceuticals, MAY 27, 2014, View Source [SID:1234500554] & Blood. 2014 May 22;123(21):3239-46. doi: 10.1182/blood-2013-12-540971. Epub 2014 Mar 31. View Source). The study manuscript entitled “Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML” appears in the May 22, 2014 issue.
These data, along with results from the Phase 2 study of CPX-351 in patients with AML in first relapse, support Celator’s currently-enrolling Phase 3 study of CPX-351 as a first-line therapy in older patients with high-risk (secondary) AML, which is being conducted in partnership with The Leukemia & Lymphoma Society.
This randomized, controlled, Phase 2 study evaluated 126 patients, aged 60-75 years, from 18 clinical centers in the U.S. and Canada, with newly diagnosed, pathologically confirmed AML. Patients were randomized 2:1 to receive first-line CPX-351 (100 u/m2; days 1, 3, and 5 by 90 minute infusion) or the 7+3 regimen (cytarabine 100 mg/m2/day by continuous infusion for 7 days and daunorubicin 60 mg/m2 on days 1, 2, and 3). The primary endpoint for the study was complete response (CR + CRi) and secondary endpoints included CR+CRi duration, event-free survival and overall survival.
Results showed that CPX-351 treatment was associated with higher complete response rate (66.7% vs. 51.2%; P = 0.07), prolonged event-free survival (median 6.5 vs. 2.0 months) and overall survival (median 14.7 vs. 12.9 months). Ten patients with persistent AML after treatment with 7+3 crossed over to receive CPX-351 as salvage therapy with four achieving response (3 CR + 1 CRi). All four responders survived more than one year and this potentially confounds interpretation of the overall survival data.
A planned analysis of secondary AML patients (patients with a prior antecedent hematologic disorder or history of prior cytotoxic treatment) showed an improved response rate (57.6% vs 31.6%, P=0.06), prolonged event-free survival (median 4.5 vs. 1.3 months, HR=0.59, P=0.08) as well as overall survival (median 12.1 vs. 6.1 months, HR=0.46, P=0.01). The overall survival benefit in this population was statistically significant.
Treatment with CPX-351 was associated with well-characterized and manageable adverse events. Recovery from cytopenias was longer following CPX-351 (median days to ANC ≥1000: 36 vs. 32; Platelets > 100K: 37 vs. 28) with more grade 3-4 infections but without an increase in infection-related deaths (3.5% vs. 7.3%) or 60-day mortality (4.7% vs. 14.6%), indicating acceptable safety.