IBCL-094: Combination of Ibrutinib with Rituximab Versus Placebo with Rituximab for First-Line Treatment of Follicular Lymphoma: PERSPECTIVE, a Randomized Phase 3 Study

Context: Few first-line chemotherapy-free treatment options are available for patients with follicular lymphoma (FL) who are elderly or have comorbid conditions. Single-agent rituximab has been used to treat previously untreated elderly, frail patients or those with low tumor burden. Ibrutinib, a once-daily Bruton's tyrosine kinase inhibitor, is approved in the US and EU for the treatment of various B-cell malignancies. The combination of once-daily ibrutinib with 4 weekly doses of intravenous rituximab was evaluated in a phase 2 study as a first-line treatment option for patients with FL. At a median follow-up of 34 months, an overall response rate of 85% and complete response of 40% were reported. At 30 months, the progression-free survival (PFS) and overall survival rates were 67% and 97%, respectively (Fowler, BJH. 2020). Based on these promising results, the phase 3 PERSPECTIVE study was designed to further evaluate ibrutinib-rituximab combination therapy in previously untreated patients with FL. Objective: To compare PFS outcomes between: (1) ibrutinib-rituximab and placebo-rituximab, and (2) continuous versus fixed-duration ibrutinib treatment. Design: Phase 3, multicenter, randomized, double-blind, placebo-controlled study (PCYC-1141-CA, NCT02947347 ). Patients or other participants: Eligible patients are enrolled if they meet ≥1 Groupe d'Etude des Lymphomes Folliculaires (GELF) criterion, and are aged ≥70 years or 60–69 years with ≥1 comorbidities (creatinine clearance 30–59 mL/min or ECOG performance status of 2). Patients who received any prior treatment for FL or showed evidence of CNS involvement or transformed lymphoma are excluded. Enrollment of approximately 440 patients is planned. Interventions: In Part 1, patients will be randomized to receive either: (1) once-daily oral ibrutinib-rituximab, or (2) once-daily oral placebo-rituximab. Patients in both arms will receive rituximab in 4 weekly doses, followed by rituximab maintenance therapy. In Part 2, patients receiving ibrutinib-rituximab and remaining on ibrutinib treatment for ≥2 years will be randomized again to either receive once-daily oral ibrutinib or switch to once-daily oral placebo. Main outcome measures: The primary endpoint is PFS for both parts. Conclusions: The study is currently enrolling patients at participating sites in the US, EU, and Asia Pacific. Funding: Pharmacyclics LLC, an AbbVie Company.