Clinical Study of Oncolytic Vaccinia VIrus Delivering Targeted CD19 in Vivo CAR-T/M Therapy for Refractory/Relapsed B-cell Lymphoma

Exploratory Study of Oncolytic Vaccinia VIrus-Delivered Targeted CD19 In Vivo CAR-T/M Therapy for Refractory/Relapsed B-Cell Lymphoma

NCT07398963•Second Affiliated Hospital, School of Medicine, Zhejiang University

View on ClinicalTrials.gov

Summary

To study the safety and effectiveness of oncolytic Vaccinia VIrus-Delivered Targeted CD19 In Vivo CAR-T/M Therapy for Refractory/Relapsed B-Cell Lymphoma

Detailed Description

This is a single-arm, dose-escalation, non-randomized, multicenter, dose-escalation exploratory study aimed at evaluating the safety and efficacy of a novel CD19-CAR oncolytic vaccinia virus (RGV005) in patients with B-cell lymphoma. The study included two groups: (1) intratumoral injection group (12-24 patients); (2) intravenous injection group (12-24 patients). A standard 3×3 design will be used to conduct a single-dose escalation safety and tolerability trial. Patients will be assigned to one of four dose groups in ascending order: Dose Group 1 (1×10\^8 pfu), Dose Group 2 (3×10\^8 pfu), Dose Group 3 (1×10\^9 pfu), and Dose Group 4 (3×10\^9 pfu). Each dose group plans to recruit 3 subjects. After completing the treatment and the month-3 assessment visit, subjects will enter the long-term follow-up period, which will last for 3 years after administration for each patient.

Eligibility

Age

18 - 75 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Age≥ 18 years old, up to 75 years old, male or female;
•2. ECOG score 0-2;
•3. Histologically confirmed non-Hodgkin B-cell lymphoma (NHL) \[diagnostic criteria are WHO2008\], including diffuse large B-cell lymphoma (DLBCL) non-specific, primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), transformed follicular cell lymphoma (TFL) and other indolent B-cell NHL transformed types;
•4. CD19 positive (immunohistochemistry or flow cytometry);
•5. DLBCL refractory or relapse is defined as: complete remission after 2 lines of therapy; Disease progression during any course of treatment, or disease stabilization time equal to and less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation;
•6. MCL: Complete remission after 2 lines of treatment (including BTK inhibitors); Disease progression during any course of treatment, or disease stabilization time equal to and less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation;
•7. At least one measurable superficial lesion, requiring any length diameter of lymph node lesion greater than 1.5cm or any length diameter of extranodal lesion greater than 1.0cm, and uptake of the lesion on PET-CT scan (SUV greater than hepatic blood pool);
•8. Absolute peripheral blood neutrophil ≥ 1000/mm3, platelet ≥ 50,000/mm3;
•9. Heart, liver and kidney function: creatinine \<1.5mg/dL; ALT (alanine aminotransferase)/AST (aspartate aminotransferase) less than 2.5 times the upper limit of normal; Total bilirubin \< 1.5 mg/dL; Cardiac ejection fraction (EF) ≥ 50%;
•10. Have sufficient understanding ability and voluntarily sign the informed consent form;
+2 more criteria

Exclusion Criteria

•1. History of other tumors;
•2. Vaccination with the smallpox vaccine within 3 months before or during the study treatment;
•3. Receiving gene therapy or any type of oncolytic virus therapy within 3 months before the study treatment;
•4. Other open wounds;
•5. Active autoimmune diseases;
•6. Uncontrolled active infections;
•7. HIV infection, uncontrolled HBV, HCV, or syphilis infection;
•8. Known central nervous system lymphoma;
•9. Clinically significant heart disease;
•10. Allergy to albumin or egg products;
+5 more criteria

Locations (1)

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Key Dates

Start Date

February 1, 2026

Primary Completion Date

July 1, 2029

Completion Date

October 1, 2029

Last Updated

February 10, 2026

Enrollment

ESTIMATED participants

Conditions

Refractory/Relapsed B-cell Lymphoma

Interventions

CD19-CAR novel oncolytic vaccinia virus

BIOLOGICAL

Contacts

Wenbin Qian， Professor

CONTACT

+8613605801032 qianwb@zju.edu.cn