Phase IbII Study of Pembrolizumab, Ibrutinib, and Rituximab for Treating Refractory or Relapsed Primary Central Nervous System Lymphoma in Adults

What this Trial Is About

Researchers are evaluating a combination of three drugsPembrolizumab, Ibrutinib, and Rituximabas possible treatments for people with recurrent or refractory primary central nervous system lymphoma PCNSL. This open-label, multi-center Phase IbII trial aims to assess the safety and appropriate dosing in Phase Ib, then further study safety and effectiveness in Phase II. These drugs are investigational for PCNSL but approved for other lymphoma types, with Pembrolizumab designed to block tumor growth signals, Ibrutinib targeting proteins that help lymphoma cells survive, and Rituximab supporting the immune system to attack lymphoma cells. During Phase 1b, participants receive escalating doses of Ibrutinib orally twice daily starting at 560 mg, possibly increasing to 840 mg, combined with Pembrolizumab given intravenously every 3 weeks and Rituximab given intravenously once weekly for 4 weeks. In Phase 2, participants receive the established Ibrutinib dose daily, with the same schedules for Pembrolizumab and Rituximab. Treatment continues for up to 2 years unless serious side effects occur or the disease worsens. Participants will undergo screening to confirm eligibility before starting treatment. Throughout the study, researchers will perform regular evaluations including lab tests and imaging to monitor safety and disease status. After completing treatment, participants will be followed every 3 months for life to track progression-free survival at 6 months and other outcomes such as adverse events, response rates, and overall survival. The study is funded by Merck & Co., Inc. and led by the Dana-Farber Cancer Institute.

Pembrolizumab, Ibrutinib and Rituximab in PCNSL