Zanubrutinib Monotherapy in Relapsed/Refractory Central Nervous System Lymphoma

Inclusion Criteria: Key inclusion criteria: 1. Able to understand and willing to sign a written informed consent document 2. Men and woman at least 18 years of age on the day of consenting to the study 3. Histologically documented DLBCL. 4. Relapsed/refractory PCNSL or relapsed/refractory SCNSL 5. Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI or the brain or head CT) prior to study enrollment. For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells and/or imaging findings consistent with CSF disease prior to study enrollment. 6. An ECOG performance status≤2 7. Adequate bone marrow and organ function shown by: (1) Neutrophils ≥ 0.75 x 109/L independent of growth factor support within 7 days of study entry (2) Platelets ≥ 50 x 109/L independent of growth factor support or transfusion within 7 days of study entry (3) Creatinine clearance of ≥ 30 mL/min (4) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (5) Bilirubin ≤ 1.5 x ULN (6) International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN. 8\. Recovered to grade 1 toxicity from prior therapy before the first dose of study drug 9. Agree to use highly effective methods of birth control during the period of therapy and for 3 months after the last dose of the study drug. Exclusion Criteria: 1. Patients with SCNSL actively receiving treatment for extra-CNS disease 2. Concurrently using other approved or investigational antineoplastic agents 3. Prior chemotherapy, targeted therapy, or radiation therapy within 4 weeks 4. Prior exposure to a BTK inhibitor 5. Concurrently using more than 8mg of dexamethasone daily or the equivalent 6. History of other active malignancies within 2 years of study entry 7. Major surgery within 4 weeks of screening or not recovered from the side effects of such surgery 8. Known to have human immunodeficiency virus (HIV) infection 9. Known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests 10. Active infection systemic including infections requiring oral or intravenous antimicrobials 11. Currently active clinically significant cardiovascular disease 12. QTcF \> 480 msecs or other significant electrocardiogram (ECG) abnormalities 13. Unable to swallow capsules or disease significantly affecting gastrointestinal function 14. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could have compromised the patient's safety, or put the study at risk 15. Required ongoing treatment with medication that are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers 16. History of stroke or intracranial hemorrhage within 6 months prior to enrollment 17. Inability to comply with study procedures 18. Pregnant or lactating women 19. Prior allogenic hematopoietic stem cell transplantation (autologous stem cell transplant is NOT an exclusion)