Both orelabrutinib and sintilimab are promising classes of therapy for central nervous system lymphoma. Given the poor outcomes and limited options for relapsed or refractory central nervous system lymphoma. The investigators seek to evaluate the efficacy and toxicity of the combination of orelabrutinib with sintilimab in this patient population.~Phase 1b (maximum 12 total cycles) Orelabrutinib dose escalation will occur using a standard 3+3 dose-escalation approach to determined the maximum tolerated dose(MTD) of orelabrutinib dose in combined regimen, beginning at dose level I (150 mg daily) and potentially escalating to dose level 2 (200mg) and dose level 3 (250mg) with rules for escalation and de-escalation. If the dose-limiting toxicity is not found, the dose of 250mg qd will be used for phase II trial.~Orelabrutinib: orally daily Sintilimab: The dose of sintilimab is fixed dose. 200 mg intravenously every 3 weeks (maximum 12 total dose)~Phase 2 Participants will receive orelabrutinib and sintilimab at the pre-determined dosage level established in Phase 1b, until progression of the disease (PD), unacceptable toxicity, or patient/investigator discretion. The response will be evaluated every 2 cycles.~Orelabrutinib: orally maximum tolerated dose from phase 1b daily (150 mg or 200 mg or 250mg) Sintilimab: The dose of sintilimab is fixed dose. 200 mg intravenously every 3 weeks
This phase Ib/II trial is evaluating the efficacy and side effect of orelabrutinib and sintilimab as possible treatments for relapsed or refractory central nervous system lymphoma.