A Clinical Study on the Efficacy and Safety of Methotrexate (MTX) or Thiotepa (for MTX Intolerance) or Temozolomide (TMZ) Combined With Orelabrutinib and Selinexor in Relapsed/Refractory Primary or Secondary Central Nervous System Lymphoma（SELINA）

Clinical Study on the Efficacy and Safety of Methotrexate (MTX) or Thiotepa (for MTX intolerance) or Temozolomide (TMZ) Combined with Orelabrutinib and Selinexor in the Treatment of Relapsed/Refractory Primary or Secondary Central Nervous System Lymphoma This study adopts an open-label, prospective, single-arm, single-center design aimed at evaluating the efficacy and safety of methotrexate (MTX) or thiotepa (for MTX intolerance) or temozolomide (TMZ) combined with orelabrutinib and selinexor in the treatment of relapsed/refractory primary or secondary central nervous system lymphoma (r/r CNSL). Primary Objective To evaluate the efficacy and safety of methotrexate (MTX) or thiotepa (for MTX intolerance) or temozolomide (TMZ) combined with orelabrutinib and selinexor in the treatment of relapsed/refractory primary or secondary central nervous system lymphoma (r/r CNSL). Secondary Objective To assess the benefit-risk balance of methotrexate (MTX) or thiotepa (for MTX intolerance) or temozolomide (TMZ) combined with orelabrutinib and selinexor in combination with chemotherapy in the clinical management of relapsed/refractory primary or secondary central nervous system lymphoma (r/r CNSL). Patients with relapsed/refractory primary or secondary CNSL (PCNSL/SCNSL) who meet the inclusion criteria will be enrolled. Previous study data indicate that the combination of orelabrutinib with methotrexate or temozolomide in the treatment of relapsed/refractory central nervous system lymphoma can achieve an ORR of 60%. It is anticipated that the addition of selinexor will increase the ORR to 75%. The treatment effect in r/r CNSL patients is expected to be superior to that of chemotherapy-based combination regimens (one-sided test). With a one-sided alpha = 0.025, beta = 0.1, and an expected enrollment completion within 12 months, along with a follow-up period of 24 months, the planned sample size is 23 patients. Accounting for a 10% dropout rate, the corrected sample size for t