Successful Addition of a New Treatment Arm to the Phase III FLAIR Trial in CLL
Posted: Friday, March 19, 2021
The multicenter phase III FLAIR trial was designed to determine whether the progression-free survival benefit was greater with ibrutinib plus rituximab versus fludarabine and cyclophosphamide plus rituximab in patients with untreated chronic lymphocytic leukemia (CLL). According to Dena R. Howard, PhD, of the University of Leeds, United Kingdom, and colleagues, during recruitment, early evidence suggested that ibrutinib plus venetoclax may be another promising treatment combination in this population. The trial framework was successfully amended to include this combination after 2 years and 10 months of the planned recruitment period. The methodology was described in the journal Trials.
“FLAIR is an exemplar of how an emerging experimental therapy can be assessed within an existing trial structure without compromising the conduct, reporting, or validity of the trial,” the investigators remarked. “This strategy offered considerable resource savings and allowed the new experimental therapy to be assessed within a confirmatory trial in the United Kingdom years earlier than would have otherwise been possible.”
Originally, FLAIR was designed as a two-arm trial requiring 754 patients. New experimental and control arms were added during stage 2. In stage 3, the original experimental arm was closed after it reached its planned recruitment target. A total of 1,516 patients will be randomly assigned to a treatment arm.
Recruitment was not paused when changes to the protocol and randomization schedule were made. After peer review by oversight committees, Cancer Research UK, ethical and regulatory committees, and pharmaceutical partners, the statistical considerations to ensure the results for the original and new hypotheses were unbiased were approved; they included the use of concurrent comparators in the case of any stage effect, consideration of analysis methods across trial stages, and appropriate control of the type I error rate. The operational aspects of successfully implementing the amendments included gaining approvals and additional funding, data-management requirements, and implementation at treatment centers.
Disclosure: For full disclosures of the study authors, visit trialsjournal.biomedcentral.com.