Clinical Trial Radar

1. History of primary or secondary central nervous system (CNS) lymphoma or CNS lymphoma involvement.

2. Current or previous diagnosis of the following lymphoma subtypes: primary CNS DLBCL, primary mediastinal (thymic) large B-cell lymphoma, primary effusion DLBCL, double-hit DLBCL with BCL2 and MYC rearrangements, B-cell lymphoma unclassifiable with features intermediate between DLBCL and classic Hodgkin lymphoma/Burkitt lymphoma (gray-zone lymphoma), primary cutaneous DLBCL, indolent lymphoma, Burkitt lymphoma, EBV-positive mucocutaneous ulcer, DLBCL associated with chronic inflammation, lymphomatoid granulomatosis, intravascular large B-cell lymphoma, ALK-positive large B-cell lymphoma, plasmablastic lymphoma, HHV8-positive DLBCL NOS, primary testicular lymphoma.

3. Transformed lymphoma derived from other lymphoma types, including follicular lymphoma, marginal zone B-cell lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma.

4. Previous organ transplantation or hematopoietic stem cell transplantation.

5. Other malignancy diagnosed within 5 years prior to the first dose or concurrent malignancy, **except**:

   other malignancy treated with surgery alone and achieving disease-free survival (DFS) for 5 consecutive years; cured carcinoma in situ of the cervix, non-melanoma skin cancer, and superficial bladder cancer \[Ta (non-invasive tumor), Tis (carcinoma in situ), T1 (tumor invades lamina propria)\].

6. Previous treatment with cytotoxic agents for other diseases (e.g., rheumatoid arthritis) within 5 years prior to the first dose, or previous use of any anti-CD20 antibody.

7. Previous use of any monoclonal antibody within 3 months prior to the first dose.

8. Participation in another interventional clinical trial within 3 months prior to the first dose.

9. Known hypersensitivity or contraindication to any study intervention, including:

   • Contraindications to celecoxib, including hypersensitivity to celecoxib (e.g., known sulfonamide allergy, history of asthma, urticaria, or other allergic reactions induced by NSAIDs);
   • Active peptic ulcer or gastrointestinal bleeding;
   • Known hypersensitivity to rituximab or murine monoclonal antibody products;
   • Contraindication to any component of the CHOP regimen, including previous anthracycline therapy;
   • Diabetic patients unable to tolerate prednisone in the regimen.

10. Use of glucocorticoids > 30 mg/day prednisone or equivalent for indications other than lymphoma symptom control:

    - If receiving corticosteroid therapy ≤ 30 mg/day prednisone or equivalent, a stable dose must be documented for at least 4 weeks before Cycle 1 Day 1;

    - If urgent glucocorticoid therapy (up to 100 mg prednisone or equivalent for a maximum of 7 days, Days -7 to -1) is required for lymphoma symptom control before the first dose, all tumor assessments must be completed before glucocorticoid initiation.

    Major surgery (excluding diagnostic procedures) within 1 month prior to randomization.

11. Severe peripheral or central nervous system disease, e.g., history of progressive multifocal leukoencephalopathy.

12. Previous anti-DLBCL therapy, including chemotherapy, targeted therapy, immunotherapy, definitive radiotherapy with curative intent (except palliative non-curative radiotherapy), or surgical treatment (except biopsy).

13. Adverse events from prior therapy not resolved to ≤ CTCAE Grade 1 (except Grade 2 peripheral neuropathy, alopecia, hypothyroidism controlled by hormone replacement, or type 1 diabetes mellitus well controlled with insulin).

14. Administration of live attenuated viral vaccine within 1 month prior to enrollment.

15. Uncontrolled infection (i.e., clinically unstable) requiring parenteral antibiotics, antivirals, or antifungals within 7 days before the first dose; prophylactic use is permitted.

16. Active HBV infection or active HCV infection. Patients with controlled HBV/HCV may be included cautiously at the investigator's discretion after effective antiviral intervention.

17. HIV infection and/or acquired immunodeficiency syndrome.

18. Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may interfere with study drug absorption.

19. Significant cardiovascular disease, including any of the following:

    - Cardiac insufficiency ≥ NYHA Class II, or LVEF < 50% by echocardiography;

    - History of clinically significant ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or arrhythmia requiring continuous antiarrhythmic therapy;

    - Myocardial infarction, serious arrhythmia, or unstable angina within 6 months before the first dose;

    - History of clinically significant QTc prolongation, or QTc interval > 470 ms (females) / > 450 ms (males) at screening;

    - Other cardiovascular disease deemed inappropriate by the investigator;

    • Uncontrolled hypertension despite combination therapy with 2 antihypertensive agents (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg on at least 2 measurements).

20. Pulmonary fibrosis or interstitial pneumonia (except radiologic interstitial changes without symptoms or functional impairment), or history of pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or severe pulmonary dysfunction.

21. Arterial or venous thrombotic event within 6 months before the first dose, including cerebrovascular accident (cerebral hemorrhage, cerebral infarction, transient ischemic attack), deep vein thrombosis, pulmonary embolism.

Patients with intermuscular vein thrombosis or infusion port-related thrombosis may be included if deemed low risk by the investigator.

22. Renal failure requiring hemodialysis or peritoneal dialysis, or history of nephrotic syndrome.

23. Current or previous autoimmune disease requiring treatment, except hypothyroidism on stable replacement therapy and type 1 diabetes mellitus.

24. History of alcoholism or drug abuse. 25. Any other serious or unstable medical condition (other than excluded malignancies), psychiatric disorder, or condition that may compromise patient safety, informed consent, or compliance with study procedures, in the investigator's judgment.

26. Pregnant or breastfeeding female patients, or fertile patients unwilling to use effective contraception.

27. Patients deemed ineligible for the study by the investigator.

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