Zanubrutinib With Pemetrexed to Treat Relapsed/Refractory Primary and Secondary Central Nervous System (CNS) Lymphomas

This study is testing a combination of two drugs — zanubrutinib (a targeted oral drug) and pemetrexed (a chemotherapy) — for patients with brain lymphoma (primary or secondary CNS lymphoma) that has relapsed or not responded to prior treatment, or who could not tolerate standard high-dose therapy. **You may be eligible if...** - You have confirmed B-cell lymphoma in the brain or eye (primary CNS lymphoma or CNS involvement from another lymphoma) - Your lymphoma has progressed after prior treatment or you could not tolerate it - You are in reasonable functional health and have adequate blood counts and organ function - Your life expectancy is at least 2 months **You may NOT be eligible if...** - You have active lymphoma outside the brain or eye (systemic disease) - You have previously been treated with pemetrexed or a BTK inhibitor (like ibrutinib or acalabrutinib) - You have serious uncontrolled infections, autoimmune conditions, or bleeding disorders - You have had a recent stroke, brain bleed, or blood clot - You are pregnant or breastfeeding - You have had an organ transplant or need ongoing immunosuppression Talk to your doctor to see if this trial is right for you.