This is a prospective, single-Arm, phase II clinical study evaluating the efficacy and safety of thiotepa in combination with pirtobrutinib (a BTK Inhibitor) and sintilimab (a PD-1 Inhibitor) for frail or relapsed/refractory primary or secondary central nervous system lymphoma.It includes screening phase， induction therapy phase, and maintenance therapy phase.The screening period is defined as within 14 days prior to the first dose.Induction Treatment Phase: Enrolled subjects will receive a combination regimen of thiotepa, pirtobrutinib, and sintilimab. Treatment is administered in 21-day cycles for up to 6 cycles. Patients who achieve a disease response may proceed to consolidation therapy with either autologous hematopoietic stem cell transplantation or whole-brain radiotherapy at the investigator's discretion.Maintenance Treatment Phase: For patients who do not receive consolidation therapy with autologous transplantation or whole-brain radiotherapy, maintenance treatment with pirtobrutinib plus sintilimab will be initiated (for up to 1 year). Patients who receive any consolidation therapy will not proceed to maintenance treatment.Treatment response will be assessed throughout the study using the International Primary CNS Lymphoma Collaborative Group (IPCG) criteria. The trial will monitor patient survival data, objective response rate (ORR), and safety parameters.Upon discontinuation of study treatment or completion of the 1-year treatment period, subjects will enter the follow-up phase. During follow-up, radiographic assessments (contrast-enhanced CT of the involved site is recommended) will be performed according to the following schedule: every 3 months for the first 2 years, every 6 months from Year 3 to Year 5, and annually after 5 years, until the end of the follow-up period. For subjects who have not withdrawn consent, survival information (including date and cause of death, subsequent anti-tumor therapies, etc.) will be collected every 3 months via telephone and/or clinical visit.
Histopathologically confirmed relapsed primary central nervous system lymphoma (PCNSL) of B-cell lineage, or secondary central nervous system lymphoma (SCNSL) with a previously confirmed B-cell origin primary lesion but without evidence of active extracranial systemic involvement.
The patients or their legal guardians provide voluntary written informed consent.
Age>=18 years, both male and female.
Karnofsky Performance Status (KPS) score>=40.
The patients with secondary central nervous system lymphoma (SCNSL) who have lesions outside the CNS and require systemic treatment.
Received chemotherapy, radiotherapy, immunotherapy or antibody-based treatments for anti-tumor purposes within 4 weeks prior to the first administration (or within 5 half-lives), those who had used small molecule targeted drugs or traditional Chinese medicine with anti-tumor indications within 2 weeks, and those who had received monoclonal antibody conjugate drug treatments within 10 weeks.
Receipt of any vaccine (including but not limited to vaccines for COVID-19, influenza, pneumonia, shingles, hepatitis B, etc.) within 4 weeks before taking the medicine for the first time.
Concurrent enrollment in another interventional clinical study, or less than 4 weeks between the last dose of prior clinical trial treatment and the first dose in this study.
Single group
Thiotepa, Pirtobrutinib , Sintilimab(TPS)
DrugInduction Phase: Drug: Pirtobrutinib • Dose:200mg, d1-21, Drug: Thiotepa • Dose: 40mg/m², d1, Drug: Sintilimab • Dose: 200mg，d1. Maintenance Phase: Drug: Pirtobrutinib • Dose:200mg, d1-21, Drug: Sintilimab • Dose: 200mg，d1.
ORR
Objective Response Rate
CRR
Complete Remission Rate
PRR
Partial Remission Rate
PFS
Progression Free Survival
OS
Overall Survival
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