An Open-Label Expanded-Access Trial of Bendamustine in Patients with Rituximab-Refractory Indolent Non-Hodgkin Lymphoma or Previously Untreated Chronic Lymphocytic Leukemia: BEND-ACT

Background: Bendamustine is a bifunctional alkylating agent with unique properties that distinguish it from other agents in its class. Bendamustine is used as monotherapy or in combination with other agents to treat patients with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Methods: The prospective interventional open-label BEND-ACT trial evaluated bendamustine in patients with rituximab-refractory indolent NHL (iNHL) and previously untreated CLL. Study objectives were to assess the safety and tolerability of bendamustine monotherapy and to provide patients with access to bendamustine before Health Canada approval. The study aimed to enrol up to 100 patients. All patients with iNHL received an intravenous dose of bendamustine 120 mg/m² over 60 minutes on days 1 and 2 for up to eight 21- or 28-day treatment cycles. All patients with CLL received an intravenous dose of bendamustine 100 mg/m² over 30 minutes on days 1 and 2 for up to six 28-day treatment cycles. Results: Of 90 patients treated on study (16 with CLL and 74 with iNHL), 35 completed the study (4 with CLL and 31 with iNHL). The most common treatment-emergent adverse events (TEAES) were nausea (70%), fatigue (57%), vomiting (40%), and diarrhea (33%)—mostly grades 1 and 2. Ondansetron was the most common supportive medication used in the patients (63.5% of those with iNHL and 68.8% of those with CLL). Neutropenia (32%), anemia (23%), and thrombocytopenia (21%) were the most frequent hematologic TEAES, with neutropenia being the most common grade 3 or 4 TEAES leading to dose modification. Dose delays occurred in 28 patients (31.3%) because of grade 3 or 4 TEAES, with a higher incidence of dose delays being observed in iNHL patients on the 21-day treatment cycle than in those on the 28-day treatment cycle (50.0% vs. 24.1%). During the study, 33 patients (36.7%) experienced at least 1 serious adverse event, and 4 deaths were reported (all in patients with iNHL). Conclusions: The type and frequency of the TEAES reported accorded with observations in earlier clinical trials and post-marketing experiences, thus confirming the acceptable and manageable safety profile of bendamustine.