title: 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.
abstract: 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/m(2) 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/m(2) 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 teae 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.
authors: Department of Oncology, McMaster University, and Juravinski Cancer Centre and Hospital, Hamilton, ON;
authors: C T
authors: CT
authors: Kouroukis
authors: Department of Medical Oncology and Hematology, University of Toronto, Toronto, ON;
authors: M
authors: M
authors: Crump
authors: Dalhousie University and QEII Health Sciences Centre, Halifax, NS;
authors: D
authors: D
authors: MacDonald
authors: Hematology-Oncology, CHU de Québec, Hôpital Enfant-Jésus, Montreal, QC;
authors: J F
authors: JF
authors: Larouche
authors: Department of Oncology and Medicine, University of Calgary, and Tom Baker Cancer Centre, Calgary, AB;
authors: D A
authors: DA
authors: Stewart
authors: Department of Internal Medicine, University of Manitoba, and Cancer Care Manitoba, Winnipeg, MB;
authors: J
authors: J
authors: Johnston
authors: Lundbeck Canada Inc., Montreal, QC;
authors: S
authors: S
authors: Sauvageau
authors: Lundbeck Canada Inc., Montreal, QC;
authors: E
authors: E
authors: Beausoleil
authors: Lundbeck Canada Inc., Montreal, QC;
authors: P
authors: P
authors: Sage
authors: Lundbeck Canada Inc., Montreal, QC;
authors: S G
authors: SG
authors: Dubois
authors: New Evidence, Toronto, ON;
authors: A
authors: A
authors: Christofides
authors: New Evidence, Toronto, ON;
authors: S
authors: S
authors: Di Clemente
authors: University of British Columbia and BC Cancer Agency, Vancouver, BC.
authors: L
authors: L
authors: Sehn
keywords: Clinical trials; bendamustine; chronic lymphocytic leukemia; expanded-access; indolent non-Hodgkin lymphoma; open-label; safety