Actively Recruiting
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
Led by Zhejiang Cancer Hospital · Updated on 2026-02-18
24
Participants Needed
1
Research Sites
233 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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 For subjects who have not withdrawn consent, survival information (including date and cause of death, subsequent anti-tumor therapies, etc.)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.
CONDITIONS
Official Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histopathologically confirmed relapsed primary CNS lymphoma of B-cell lineage or secondary CNS lymphoma with B-cell origin without active extracranial disease
- Patients or legal guardians provide voluntary written informed consent
- Age 18 to 80 years, male or female
- Karnofsky Performance Status score of 40 or higher
- Unsuitable for methotrexate-based chemotherapy or refuse high-dose methotrexate
- Life expectancy longer than 3 months
- Parenchymal lesions >10x10 mm on MRI or leptomeningeal disease confirmed by CSF cytology and imaging within 14 days before enrollment
- Prior anti-tumor therapy toxicities recovered to Grade 1 or baseline except alopecia
- Bone marrow and organ function meeting specified hematologic, hepatic, renal, and coagulation criteria without recent supportive treatment
- Effective contraception use during study and for 3 months after treatment interruption for reproductive-age women and fertile men
- Willingness and ability to undergo multiple MRI/CT scans and lumbar puncture
- Ability to swallow oral medication without difficulty
You will not qualify if you...
- Secondary CNS lymphoma patients with lesions outside the CNS requiring systemic treatment
- Received chemotherapy, radiotherapy, immunotherapy, or antibody treatments within specified recent timeframes before first dose
- Vaccination within 4 weeks before first dose
- Concurrent enrollment in another interventional clinical study or recent prior clinical trial treatment
- History of Grade 3 or higher immune-related adverse events from thiotepa, PD-1 inhibitors, or BTK inhibitors
- Active bleeding or conditions increasing bleeding risk or requiring therapeutic anticoagulation
- Use of moderate or strong CYP3A4/5 inhibitors or inducers recently or during study
- Other malignant tumors needing anti-cancer treatment
- Uncontrolled or significant cardiovascular diseases as detailed
- Active uncontrolled infection needing intravenous antimicrobials
- Active chronic hepatitis B or C or syphilis with specific viral load limits
- Known HIV infection or AIDS
- Significant gastrointestinal issues affecting drug intake or absorption
- Recent autologous or allogeneic transplantation within specified time frames
- Pregnancy or breastfeeding
- Recent stroke or intracranial hemorrhage within 6 months
- History or presence of lung diseases like pulmonary fibrosis or radiation pneumonitis
- Kidney, nerve, liver, endocrine diseases or other conditions deemed unsuitable by investigator
- Active autoimmune diseases or history of such, with specified exceptions
- Major surgery within 28 days before first study dose
AI-Screening
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Trial Site Locations
Total: 1 location
1
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China, 310058
Actively Recruiting
Research Team
H
Haiyan Yang, MD
CONTACT
H
Haifeng Yu, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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