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;
Single group
Zanubrutinib
DrugZanubrutinib capsules will be self-administered orally by participants at a starting dose of 160 mg twice a day (BID) or 320 mg once a day (QD)\* at the beginning of Cycle 2 of Pola-R-CHP therapy.
Methotrexate
DrugParticipants will receive Methotrexate as per standard of care (SOC).
Polatuzumab Vedotin
DrugParticipants will receive Polatuzumab Vedotin as per standard of care (SOC).
Rituximab
DrugParticipants will receive Rituximab as per standard of care (SOC), as part of combination standard of care Pola-R-CHP therapy.
Cyclophosphamide
DrugParticipants will receive Cyclophosphamide as per standard of care (SOC), as part of combination standard of care Pola-R-CHP therapy.
Doxorubicin
DrugParticipants will receive Doxorubicin as per standard of care (SOC), as part of combination standard of care Pola-R-CHP therapy.
Prednisone
DrugParticipants will receive Prednisone as per standard of care (SOC), as part of combination standard of care Pola-R-CHP therapy.
Number of participants experiencing dose-limiting toxicities (DLTs)
The number of participants experiencing dose-limiting toxicities (DLTs) after starting study therapy. Toxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Overall Response Rate (ORR)
Overall response rate (ORR) is defined as the proportion of participants with complete response (CR) or partial response (PR) as the best response.
Number of Patients achieving conversion from PR to CR
Conversion from PR to CR will be assessed by the number of patients achieving an initial PR followed by how many will achieve a subsequent CR by Lugano response criteria. Partial response (PR) will be calculated by a Deauville score of 4 or 5 with reduced uptake from baseline, and complete response (CR) is defined as a Deauville score of ≤ 3.
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the elapsed time in years from the start of treatment until disease progression or death, whichever is earlier. Participants who remain alive without progression will be censored at the last documented disease assessment date.
Overall Survival (OS)
Overall survival (OS) is defined as the elapsed time in years from the start of treatment until death from any cause. Alive participants will be censored at the last date known to be alive.
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