The purpose of this study is to is to determine the effects (good and bad) of Zanubrutinib in Combination with Pola-R-CHP and High-dose Methotrexate in patients with Secondary Central Nervous System (CNS) Lymphoma.
Men and women ≥ 18 years of age on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place).
Patients must have histologic confirmation of large B-cell lymphoma (LBCL) defined by the World Health Organization (WHO) classification. All LBCL subtypes are acceptable. Note: Patients with prior treatment for indolent lymphoma are still eligible for participation as long as they did not receive anthracycline-based therapy.
Baseline 18-fluorodeoxyglucose (FDG)-positron emission tomography scan/computed tomography (PET/CT) must demonstrate FDG avid lesions compatible with CT-defined anatomical tumor sites (Note: FDG-PET/CT is not mandatory, and patients with CT scans only will be eligible for study entry as well). Patients should have at least 1 measurable site of disease per Lugano classification in FDG-PET/CT or CT scans.
Presence of systemic and CNS involvement (brain, cerebellum, brainstem, meninges, cranial nerves, eyes, spinal cord, or a combination of these) at presentation.
Primary CNS lymphoma without evidence of systemic lymphoma.
Prior systemic lymphoma therapy (Note: 1 cycle of an anthracycline based regimen, such as rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP), polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP), dose-adjusted etoposide phosphate, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin, and rituximab (EPOCH-R), or rituximab, cyclophosphamide, vincristine, doxorubicin, and methotrexate (R-Codox-M), and/or 1 dose of intrathecal therapy, will be allowed before enrollment [Section 5.9]). Note: Patients with prior treatment for indolent lymphoma are still eligible for participation as long as they did not receive anthracycline-based therapy.
Myocardial infarction within 6 months before screening;
Unstable angina within 3 months before screening;