Brentuximab Vedotin Combined With R-CHP in Newly Diagnosed EBV+ DLBCL-NOS

Nanjing Medical University

Status and phase

Not yet enrolling

Phase 2

Conditions

Brentuximab Vedotin

EBV-Positive Diffuse Large B-Cell Lymphoma, Nos

Treatments

Drug: BV+R-CHP

Study type

Interventional

Funder types

Other

Identifiers

NCT06925555

2025-SR-050

Details and patient eligibility

About

Evaluation of the Safety and Efficacy of Brentuximab Vedotin Combined With R-CHP in Newly Diagnosed EBV+ DLBCL-NOS.

Full description

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.

Enrollment

25 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

- Patients must meet all of the following inclusion criteria to be eligible for enrollment:

BV+DLBCL, NOS diagnosed by pathological diagnosis according to WHO 2016 classification criteria;
Sign the informed consent form;
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;
ECOG Performance Status (PS) of 0-2;
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.
Expected survival ≥ 3 months.
Age 18-70 years.
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.