An interim analysis of a large phase 3 clinical trial found that the combination of ibrutinib plus rituximab was superior to standard treatment for patients age 70 and younger with previously untreated chronic lymphocytic leukemia (CLL). The trial met its primary endpoint of an improvement in progression-free survival (the length of time patients live before their disease worsens). The combination also improved overall survival, the trial’s secondary endpoint. In general, patients in the ibrutinib–rituximab arm were less likely to experience serious side effects than those in the standard treatment arm. Until now, the standard treatment for previously untreated CLL has been a six-month course of FCR, which combines the chemotherapy drugs fludarabine and cyclophosphamide with rituximab.
The data and safety monitoring board overseeing the trial, known as E1912, recommended that these results be released immediately given their significance to public health. The findings were presented as a late-breaking abstract at the American Society of Hematology (ASH) annual meeting on December 4, 2018. The trial was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and designed by researchers with the ECOG-ACRIN Cancer Research Group.
The study was conducted through NCI’s National Clinical Trials Network. Pharmacyclics LLC provided ibrutinib and clinical trial support funding under a cooperative research and development agreement with NCI and a separate agreement with ECOG-ACRIN.
CLL is one of the most common types of leukemia in adults. It typically occurs during or after middle age and rarely occurs in individuals under the age of 40. Ibrutinib and rituximab are targeted treatments.
The trial enrolled 529 patients between January 2014 and June 2016. Those enrolled in the trial were adults age 70 and younger who had never received treatment for CLL and required treatment. Patients were randomly assigned to receive either the ibrutinib–rituximab combination or FCR.
Findings from another NCI-supported trial on ibrutinib in patients with CLL were also presented at the ASH meeting and published in The New England Journal of Medicine. The A041202 trial — an international phase 3 clinical trial coordinated by the Alliance for Clinical Trials in Oncology — demonstrated that ibrutinib produces superior progression-free survival compared with standard chemoimmunotherapy (bendamustine plus rituximab) in previously untreated patients with CLL who are age 65 and older. The study found that adding rituximab to ibrutinib did not improve progression-free survival beyond ibrutinib alone.
