Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306).

PIX306 was a phase 3, randomised, single-blind, multicentre trial conducted in adult patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) grade 3 who relapsed after >= 1 rituximab-containing regimen and were not eligible for a stem cell transplant. Patients were randomised 1:1 to pixantrone 50 mg/m(2) or gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle, combined with rituximab 375 mg/m(2) on day 1, for up to six cycles. Patients were followed for up to 96 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), complete response (CR) rate, overall response rate (ORR) and safety. Overall, 312 patients were randomised (median age 73 center dot 0 years). The study did not meet its primary endpoint. Median PFS [95% confidence interval (CI)] was 7 center dot 3 months (5 center dot 2-8 center dot 4) with pixantrone + rituximab (PIX + R) and 6 center dot 3 months (4 center dot 4-8 center dot 1) with gemcitabine + rituximab [GEM + R; hazard ratio (HR): 0 center dot 85; 95% CI 0 center dot 64-1 center dot 14; P = 0 center dot 28]. Median OS was 13 center dot 3 (10 center dot 1-19 center dot 8) months with PIX + R and 19 center dot 6 (12 center dot 4-31 center dot 9) months with GEM + R (HR: 1 center dot 13; 95% CI 0 center dot 83-1 center dot 53). ORR was 61 center dot 9% and 43 center dot 9% respectively and CR rate 35 center dot 5% and 21 center dot 7%. The incidence of adverse events, including cardiac events, was not statistically significant different between PIX + R and GEM + R.