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

A Multi-center，Single-arm, Open-label Phase II Clinical Study on Brentuximab Vedotin Combined With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) in the Treatment of Newly Diagnosed EBV-positive Diffuse Large B-cell Lymphoma, Not Otherwise Specified (EBV+ DLBCL-NOS)

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

Study Overview

• Status: Not yet recruiting
• Conditions: EBV-Positive Diffuse Large B-Cell Lymphoma, Nos; Brentuximab Vedotin
• Intervention / Treatment: Drug: BV+R-CHP

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei Xu, Doctor; Phone Number: 86-2568302182; Email: xuwei10000@hotmail.com
• Study Contact Backup: Name: Liang Jinhua, M.D; Phone Number: 15952032421; Email: 1151525490@qq.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • The First Affiliated Hospital with Nanjing Medical University
      • Contact: WEI XU; Phone Number: 86-25-68302182; Email: xuwei10000@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BV+R-CHP Arm; Newly Diagnosed EBV+ DLBCL-NOS Patients Receiving Brentuximab Vedotin plus R-CHP(Rituximab、Cyclophosphamide、Doxorubicin and Prednisone)	Drug: BV+R-CHP; Brentuximab Vedotin, 1.8mg/kg/dose, d0、Rituximab, 375 mg/m2, d0、Cyclophosphamide, 750 mg/m2, d1、Doxorubicin, 50 mg/m2, d1、Prednisone, 60mg/m2, d1-5

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year progression-free survival (PFS) rate	PFS was defined as the time between inclusion and the first date of progression, relapse, or death from any cause.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	The Overall Response Rate	every 3 cycles, up to 6 cycles (each cycle is 21 days)
CR rate	complete remission rate	every 3 cycles, up to 6 cycles (each cycle is 21 days)
2-year overall survival (OS) rate	Overall Survival: from the date of inclusion to date of death, irrespective of cause	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: April 10, 2025
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 13, 2025

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 25, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Pyloric Stenosis; Gastric Outlet Obstruction; Pyloric Stenosis, Hypertrophic
• Other Study ID Numbers: 2025-SR-050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No