Phase 3 trial of pixantrone plus rituximab versus gemcitabine plus rituximab in treating relapsed/refractory transplant-ineligible aggressive non-Hodgkin's lymphoma

Abstract

Background: Aggressive non‐Hodgkin's lymphoma (NHL) comprises 44% of all NHL, and diffuse large B‐cell lymphoma (DLBCL) is the most common subtype. Anthracycline‐based regimens are the standard of care for front‐line therapy. There is currently no standard treatment for relapsed/refractory (R/R) aggressive NHL beyond second‐line for patients who are not transplant‐eligible. Pixantrone is a novel aza‐anthracenedione designed to have less cardiac toxicity than the anthracyclines. A phase 3 study of monotherapy with pixantrone versus comparator gave results that were sufficiently promising for conditional European approval for the treatment of multiply R/R aggressive B‐cell NHL. We set up a phase 3 trial to explore the efficacy of combining pixantrone with rituximab, which responds to one of the European post‐authorization measures. Trial design: We are enrolling adult patients with DLBCL or follicular grade 3 lymphoma who have relapsed after at least one multiagent chemotherapy containing rituximab. All participants are ineligible for stem cell transplantation, with Eastern Cooperative Oncology Group score ≤2 and normal cardiac function. Centers have been opened in the USA and Europe (Austria, Belgium, Bulgaria, Czech Republic, Denmark, France, Germany, Hungary, Italy, Poland, Romania, Russia, Slovakia, Spain, UK, and Ukraine). Included patients will be randomly allocated to receive up to six 28‐day cycles of pixantrone (50 mg/m2 IV on days 1, 8, 15) plus rituximab (375 mg/m2 IV on day 1) or gemcitabine (1000 mg/m2 IV on days 1, 8, 15) plus rituximab (375 mg/m2 IV on day 1). To complete 6 cycles, patients who discontinue one study drug due to toxicity may continue with the other assigned study drug. The primary endpoint is progression‐free survival; secondary endpoints include overall survival, overall response rate, and safety. Recruitment is ongoing.