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

Official title

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)

Overview

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

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.

Interventions

• 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

Primary outcome measures

• 2-year progression-free survival (PFS) rate [Time frame: 2 years]

Secondary outcome measures (3)

• ORR [Time frame: every 3 cycles, up to 6 cycles (each cycle is 21 days)]
• CR rate [Time frame: every 3 cycles, up to 6 cycles (each cycle is 21 days)]
• 2-year overall survival (OS) rate [Time frame: 2 years]

Eligibility criteria

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：

• Central nervous system (CNS) involvement.
• 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).
• History of severe allergic diseases, hypersensitivity to macromolecular protein preparations, or any component of Brentuximab Vedotin.
• Prior allogeneic organ transplant or hematopoietic stem cell transplantation.
• Concurrent systemic anti-tumor therapy during the study.
• Anti-cancer vaccines or immunostimulatory anti-tumor therapy within 3 months prior to enrollment.
• Active severe acute/chronic infection requiring systemic therapy.
• 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).
• Systemic immunosuppressive therapy within 4 weeks prior to enrollment (excluding topical/nasal/inhaled corticosteroids or physiologic doses ≤10 mg/day prednisone equivalent).
• Positive serology for HIV antibody (HIV-Ab), Treponema pallidum antibody (TP-Ab), HCV antibody (HCV-Ab); HBsAg-positive with HBV DNA >ULN.
• History of idiopathic pulmonary fibrosis or interstitial pneumonia.
• Active tuberculosis.
• Prior ≥Grade 3 immune-related adverse events from immunotherapy.
• History of neurologic/psychiatric disorders (e.g., epilepsy, dementia).
• Administration of live vaccines (e.g., influenza, varicella) within 4 weeks prior to treatment or planned during the study.
• History of alcohol/drug abuse.
• Pregnancy or lactation.
• Participation in another interventional clinical trial within 1 month prior to enrollment.
• Other factors deemed by investigators to potentially compromise efficacy/safety assessments.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital with Nanjing Medical University — Nanjing

Identifiers

NCT: NCT06925555 · 2025-SR-050

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗