First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial
Abstract
Background: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab.
Methods: Treatment-naive fit patients with chronic lymphocytic leukaemia (aged 33-81 years) without del(17p) were enrolled after undergoing a central screening process. Patients were randomly assigned (1:1) with a computer-generated randomisation list using randomly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage.
Patients were allocated to receive six cycles of intravenous fludarabine (25 mg/m2 per day) and cyclophosphamide (250 mg/m2 per day) for the first 3 days or to intravenous bendamustine (90 mg/m2 per day) for the first 2 days of each cycle. Rituximab 375 mg/m2 was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m2 during the next five cycles on day 1.
The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the standard therapy. We aimed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67.5% or less with a corresponding non-inferiority margin of 1.388 for the hazard ratio (HR) based on the 90.4% CI.
The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522.