brentuximab vedotin combined with r-chp in newly diagnosed ebv+ dlbcl-nos

Conditions: EBV-Positive Diffuse Large B-Cell Lymphoma, Nos; Brentuximab Vedotin

Summary: evaluation of the safety and efficacy of brentuximab vedotin combined with r-chp in newly diagnosed ebv+ dlbcl-nos.

ebv-positive diffuse large b-cell lymphoma, not otherwise specified (ebv+ dlbcl-nos), is an ebv-positive clonal b-cell lymphoid proliferation and circulating ebv-dna is a great indicator for prognosis among ebv associated disease.currently, there is no internationally standardized treatment regimen for ebv+dlbcl, nos. there is an urgent clinical need to explore novel effective therapeutic strategies to improve survival in this patient population.cd30 is highly expressed in ebv+dlbcl, and cd30 positivity serves as an adverse prognostic factor. brentuximab vedotin (bv), a cd30-targeted antibody-drug conjugate (adc), has shown significant improvements in progression-free survival (pfs), overall survival (os), and overall response rate (orr) compared to placebo + lenalidomide + rituximab in relapsed/refractory dlbcl patients according to the echelon-3 study.therefore, we propose a randomized, prospective, multicenter phase ii clinical trial to evaluate the efficacy (pfs, orr \[cr/cru + pr\], crr, os) and safety profile of brentuximab vedotin combined with r-chp (rituximab, cyclophosphamide, doxorubicin,prednisone) in newly diagnosed ebv+dlbcl, nos patients.

Eligibility criteria:
inclusion criteria: - patients must meet all of the following inclusion criteria to be eligible for enrollment: 1. bv+dlbcl, nos diagnosed by pathological diagnosis according to who 2016 classification criteria; 2. sign the informed consent form; 3. systemic pet/ct performed within 28 days prior to enrollment demonstrating at least one measurable lesion in two perpendicular dimensions (nodal lesion: longest diameter \>15 mm, short axis \>5 mm; extranodal lesion: longest diameter \>10 mm) per lugano 2014 criteria; 4. ecog performance status (ps) of 0-2; 5. adequate organ and bone marrow function defined as: * hematology: absolute neutrophil count (anc) ≥1.0×10⁹/l, platelet count (plt) ≥50×10⁹/l, hemoglobin (hgb) ≥8.0 g/dl; without granulocyte colony-stimulating factor, platelet transfusion, or red blood cell transfusion within 7 days prior to testing. * liver function: total bilirubin (tbil) ≤1.5×uln; alanine aminotransferase (alt) and aspartate aminotransferase (ast) ≤2.5×uln. * renal function: serum creatinine (cr) ≤1.5×uln or creatinine clearance rate (ccr) ≥50 ml/min. * cardiac function: nyha class \<iii; left ventricular ejection fraction (lvef) ≥50% by echocardiography. * coagulation: international normalized ratio (inr) ≤1.5×uln, activated partial thromboplastin time (aptt) ≤uln +10 s, prothrombin time (pt) ≤uln +3 s. * thyroid function: baseline thyroid-stimulating hormone (tsh) within normal range or abnormal tsh with normal t3/t4 levels and no clinical symptoms. 6. expected survival ≥ 3 months. 7. age 18-70 years. 8. for subjects of childbearing potential or with partners of childbearing potential: agreement to use highly effective contraception during treatment and for 90 days after the last dose. exclusion criteria: * patients who meet any of the following criteria will be excluded from the study： 1. central nervous system (cns) involvement. 2. second primary malignancy (except cured non-melanoma skin cancer, superficial bladder cancer, cervical carcinoma in situ, gastrointestinal intramucosal carcinoma, or breast cancer with no recurrence within 5 years). 3. history of severe allergic diseases, hypersensitivity to macromolecular protein preparations, or any component of brentuximab vedotin. 4. prior allogeneic organ transplant or hematopoietic stem cell transplantation. 5. concurrent systemic anti-tumor therapy during the study. 6. anti-cancer vaccines or immunostimulatory anti-tumor therapy within 3 months prior to enrollment. 7. active severe acute/chronic infection requiring systemic therapy. 8. active or history of autoimmune disease within 2 years (exceptions: vitiligo, psoriasis, alopecia, graves' disease without systemic treatment in the past 2 years; hypothyroidism requiring thyroid hormone replacement only; type i diabetes controlled with insulin). 9. systemic immunosuppressive therapy within 4 weeks prior to enrollment (excluding topical/nasal/inhaled corticosteroids or physiologic doses ≤10 mg/day prednisone equivalent). 10. positive serology for hiv antibody (hiv-ab), treponema pallidum antibody (tp-ab), hcv antibody (hcv-ab); hbsag-positive with hbv dna \>uln. 11. history of idiopathic pulmonary fibrosis or interstitial pneumonia. 12. active tuberculosis. 13. prior ≥grade 3 immune-related adverse events from immunotherapy. 14. history of neurologic/psychiatric disorders (e.g., epilepsy, dementia). 15. administration of live vaccines (e.g., influenza, varicella) within 4 weeks prior to treatment or planned during the study. 16. history of alcohol/drug abuse. 17. pregnancy or lactation. 18. participation in another interventional clinical trial within 1 month prior to enrollment. 19. other factors deemed by investigators to potentially compromise efficacy/safety assessments.