Brentuximab Vedotin, EBV-Positive Diffuse Large B-Cell Lymphoma, Nos
Conditions
Brief summary
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
DRUGBV+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
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year progression-free survival (PFS) rate | 2 years | PFS was defined as the time between inclusion and the first date of progression, relapse, or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | every 3 cycles, up to 6 cycles (each cycle is 21 days) | The Overall Response Rate |
| CR rate | every 3 cycles, up to 6 cycles (each cycle is 21 days) | complete remission rate |
| 2-year overall survival (OS) rate | 2 years | Overall Survival: from the date of inclusion to date of death, irrespective of cause |
Countries
China
Contacts
Primary ContactWei Xu, Doctor
Backup ContactLiang Jinhua, M.D
Outcome results
None listed