An independent Data and Safety Monitoring Board (DSMB) was established to review safety data collected during the study on an ongoing basis. At its meeting in December 2009, the DSMB noted a trend for increased cardiac toxicity in the experimental arm (R-CHOP + bevacizumab) compared with the control arm (R-CHOP + placebo). Additional efficacy analyses of data from 720 randomized patients were presented at a DSMB meeting on May 22, 2010; they indicated no improvement in efficacy with the addition of bevacizumab to R-CHOP. It was noted, however, that there was an apparent increase in the risk of cardiotoxicity, premature treatment withdrawal, serious adverse events (SAEs), fatal adverse events (AEs), and perforation/ulcer in the experimental arm. Based on its assessment of an increased risk with unlikely benefit for patients randomized to the experimental arm, the DSMB recommended that further enrollment in the study be permanently halted and that bevacizumab be discontinued for any patients randomized to the experimental arm. On May 31, 2010, the sponsor took the decision to stop enrollment into the study and the bevacizumab treatment was terminated with immediate effect as recommended by the DSMB.
The study protocol was amended. The primary objective of the study was changed from evaluation of efficacy to evaluation of safety and the study was extended to include an 18-month safety follow-up period. Because enrollment was terminated prematurely resulting in fewer enrolled patients than planned, the outcome measure data are premature due to fewer than expected events.
The time frame for the reporting of serious adverse events was modified. Serious adverse events (SAE) unrelated to study treatment were reported until 1 year post-treatment or until new anti-lymphoma treatment was initiated. SAEs judged to be related to study treatment and congestive heart failure events were reported at any time during the study.
