Dr. Flinn on the Design of a Phase 2 Trial of Zanubrutinib in CLL/SLL

Ian W. Flinn, MD, PhD, director of lymphoma research and a principal investigator at Sarah Cannon Research Institute, and director of the Sarah Cannon Center for Blood Cancer at Tennessee Oncology and TriStar Centennial Medical Center, discusses the design of a phase 2 trial (NCT04116437) evaluating zanubrutinib (Brukinsa) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The ongoing, single-arm, multicenter clinical trial is investigating the potential role of the novel BTK inhibitor as a treatment for patients who are intolerant to ibrutinib (Imbruvica) or acalabrutinib (Calquence). In the study, intolerance is defined as an unacceptable adverse effect (AE) for which treatment should be discontinued despite optimal supportive therapy.

After coming off of ibrutinib or acalabrutinib and once the AE resolves to grade 1 or lower, patients are eligible to receive zanubrutinib at 160 mg twice daily, explains Flinn.

The primary end point of the study is the frequency and severity of protocol-related treatment-emergent AEs, including diarrhea, myalgia, muscle spasm, arthralgia, hypertension, fatigue, rash, atrial fibrillation, and hemorrhage excluding central nervous system hemorrhage.

As zanubrutinib is a more selective BTK inhibitor, the hypothesis is that patients will be able to remain on treatment without AE recurrence, Flinn concludes.