Clinical Trial Finder

Inclusion Criteria:

1. Age ≥18 years and ≤80 years, regardless of gender; 2. Patients with pathologically confirmed, previously untreated diffuse large B-cell lymphoma (DLBCL) who are CSF-ctDNA positive for secondary CNS lymphoma (SCNSL); 3. MRI or CT of the brain showing substantial lesions in the central nervous system; patients with only meningeal lesions must have CSF cytology confirming lymphoma cells and/or imaging findings consistent with CSF examination; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3; 5. Organ function levels meeting the following requirements:Absolute neutrophil count ≥1.5×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥90g/L (if bone marrow is involved, platelets ≥50×10^9/L). 6. Liver function: ALT and AST ≤2.5 times the upper limit of normal, total bilirubin ≤2 times the upper limit of normal. 8.Renal function: creatinine ≤1.5 times the upper limit of normal; creatinine clearance rate ≥40 ml/min (assessed according to the Cockcroft-Gault formula or the estimated glomerular filtration rate [eGFR] from the Modification of Diet in Renal Disease [MDRD] formula). 9.Coagulation function: International Normalized Ratio (INR) ≤1.5 and activated partial thromboplastin time (APTT) ≤1.5×ULN. 10.Expected survival time >3 months; 11.No radiotherapy, chemotherapy, or antibody therapy within 3 weeks before medication; no targeted therapy within 10 days before medication; 12.Female subjects of childbearing potential must agree to use effective contraception during the study and for at least 90 days after the last dose of the study drug. Male subjects must be sterilized, i.e., vasectomy, or use barrier methods, while their female partners use the aforementioned effective contraception. 13.Signed written informed consent before trial screening.

Exclusion Criteria:

1. Previous treatment with BTK inhibitors; 2. Received targeted therapy within 10 days before starting the study drug, or systemic chemotherapy, radiotherapy, or antibody therapy within 3 weeks before starting the study drug; 3. Abnormal liver function (total bilirubin >2 times the normal value, ALT or AST >2.5 times the normal value), abnormal renal function (serum creatinine >1.5 times the normal value); 4. Currently have clinically significant active cardiovascular disease, such as uncontrolled arrhythmias, congestive heart failure, any grade 3 or 4 heart disease as determined by the New York Heart Association (NYHA) functional classification, or a history of myocardial infarction within 6 months before screening; 5. QTcF >450 msecs or other significant ECG abnormalities, including second-degree type II atrioventricular (AV) block or third-degree AV block; 6. Previous chemotherapy with unresolved toxicity (toxicity not resolved to ≤ grade 1 according to NCI-CTCAE 5.0, except for alopecia, absolute neutrophil count (ANC), and platelets); 7. Patients with active bleeding; 8. Patients with active infections or persistent fever within 14 days before enrollment (excluding tumor-related fever); 9. Patients with active HBV, HCV, and HIV infections; 10. Patients with serous cavity effusion; 11. Patients who have not completed 4 weeks after major organ surgery; 12. Patients receiving strong inhibitors or strong inducers of cytochrome P450 family 3 subfamily A (CYP3A); 13. Pregnant or lactating women and patients of childbearing potential who are unwilling to use contraception; 14. Patients with mental disorders/unable to obtain informed consent; 15. Patients who abuse drugs or have long-term alcoholism that affects the evaluation of trial results; 16. Patients deemed unsuitable for participation in this study by the investigator.

Arms

Other: MCD, BN2, and N1 subtypes

Other: EZB, A53, and other gene subtypes

Interventions

Drug: - R-CHOP+Z+MTX

After receiving 1 cycle of pre-treatment with the R-CHOP regimen, patients with CSF-ctDNA (+) and MCD, BN2, and N1 subtypes will receive 5 cycles of R-CHOP combined with MTX + Zanubrutinib, followed by 1 cycle of R-MTX-Zanubrutinib. After completing the above induction therapy, Patients with negative CSF-ctDNA results will continue with one more cycle of Rituximab. For patients with positive CSF-ctDNA results, the investigator will decide to continue treatment with Rituximab one more cycle combined with Temozolomide, Pomalidomide, or Lenalidomide, etc., until CSF-ctDNA turns negative. Each combined regimen consists of a 21-day treatment cycle, and efficacy will be evaluated every three treatment cycles.

Drug: - R-CHOP+MTX

After receiving 1 cycle of pre-treatment with the R-CHOP regimen, patients with CSF-ctDNA (+) and EZB, A53, and other gene subtypes will receive 5 cycles of R-CHOP combined with MTX, followed by 1 cycle of R-MTX. After completing the above induction therapy, Patients with negative CSF-ctDNA results will continue with one more cycle of Rituximab. For patients with positive CSF-ctDNA results, the investigator will decide to continue treatment with Rituximab one more cycle combined with Temozolomide, Pomalidomide, or Lenalidomide, etc., until CSF-ctDNA turns negative. Each combined regimen consists of a 21-day treatment cycle, and efficacy will be evaluated every three treatment cycles.