Orelabrutinib in Combination With Thiotepa in Refractory and Relapsed Primary CNS Lymphoma

Exclusion Criteria

• •1. The pathological diagnosis was T-cell lymphoma.
• •2. Prior therapy with a checkpoint inhibitor or BTK inhibitor.
• •3. Participation in another clinical study with an investigational product during the 12 weeks prior to the first day of study treatment.
• •4. Participants requires more than 5 mg of dexamethasone daily or the equivalent for control of primary CNS symptoms lasting for more than 5 days within 14 days.
• •5. Active bleeding within 4 weeks prior to first administration, or ongoing use of anticoagulant/antiplatelet agents, or tendency to bleeding (e.g., esophageal varices at risk for bleeding, locally active ulcerative lesions) or coagulation disorder as considered by the investigator.
• •6. Has an uncontrolled or significant cardiovascular disease, including (but not limited to) :
• •* Any of the following conditions within 6 months prior to initial administration: congestive heart failure (NYHA class III or IV), myocardial infarction, unstable angina, or arrhythmia requiring treatment at the time of screening, left ventricular ejection fraction (LVEF) \<50%;
• •* Primary or secondary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmic right ventricular cardiomyopathy, restricted cardiomyopathy, undefined cardiomyopathy);
• •* Clinical history of prolonged QTc phase, grade II type II atrioventricular block or grade III atrioventricular block or QTc interval (F method) \& GT;470 msec (female) or \>;480msec (male).
• •* Hypertension, which is difficult to control, is not suitable for this study
• •7. Uncontrolled infections or infections requiring intravenous antimicrobial treatment.
• •8. Known active infection with hepatitis C virus (HCV)，hepatitis B virus (HBV) or syphilis as determined by serologic tests and/or PCR.
• •9. History of or positive human immunodeficiency virus (HIV) screen result.
• •10. Patient underwent major systemic surgery ≤ 6 weeks prior to starting the trial treatment or who has not recovered from the side effects of such surgery, or who plan to have surgery within 2 weeks of the first dose of the study drug.
• •11. Previous organ transplantation or allogeneic stem cell transplantation.
• •12. Pregnant or lactating women, or subjects of childbearing age who do not want to use contraception for 180 days from the study period to the end of the study.
• •13. History of stroke and intracranial hemorrhage within 6 months before the first administration, except intracranial hemorrhage caused by surgical sequelae.
• •14. Patient with hepatic、renal 、neurological、psychiatric, or endocrine disease , as Investigator's discretion, is too damaged to participate in this study; Patient having other conditions that should exclude it from the trial, as the Investigator's discretion.
• •15. Alcohol or drug abuse.
• •16. Allergic to any component of the investigational product.
• •17. Participants who received live viral vaccination within 4 weeks from enrollment date. Patients are prohibited from receiving live attenuated vaccines, including influenza vaccines, during the study period.
• •18. Previous CAR-T therapy.
• •19. PVRL.