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

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

Study Overview

• Status: Recruiting
• Conditions: Refractory/Relapsed B-cell Lymphoma
• Intervention / Treatment: Biological: CD19-CAR novel oncolytic vaccinia virus

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wenbin Qian， Professor; Phone Number: +8613605801032; Email: qianwb@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The Second Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Wenbin Qian， Professor; Phone Number: +8613605801032; Email: qianwb@zju.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

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;
11. Women of childbearing potential must have a negative serum pregnancy test and agree to practice effective birth control during the treatment phase and for 60 days after the last application of oncolytic virus;
12. Male patients must agree to practice effective birth control during the study and for 60 days after the last viral treatment.

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;
11. History of organ transplantation or similar surgeries;
12. Need for systemic treatment for skin diseases;
13. History of severe systemic reactions or side effects after smallpox vaccination;
14. Known alcohol or viral dependence;
15. Pregnant or breastfeeding women.

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: intratumoral or intravenous injection RGV005; Subjects will receive intratumoral injections of CD19-CAR oncolytic vaccinia virus (RGV005)	Biological: CD19-CAR novel oncolytic vaccinia virus; Injection of CD19-CAR novel oncolytic vaccinia virus which carrying the CD19-CAR gene (RGV005) is designed to locally induce the in situ generation of CAR-T and CAR-M cells in tumors for precise lymphoma killing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicity (DLTs)	To evaluate the safety, and tolerability, and determine the recommended dosage of the CD19-CAR novel oncolytic vaccinia virus	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)		Up to 2 years
Overall response rate (ORR)		Up to 2 years
Duration of response (DOR)		Up to 2 years
Progression free survival (PFS)		Up to 2 years
Partial response rate (PR)		Up to 2 years
Complete response rate (CR)	To determine the anti-tumor effectivity of To determine the anti-tumor effectivity of the CD19-CAR novel oncolytic vaccinia virus	Up to 2 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: February 3, 2026
• First Submitted That Met QC Criteria: February 3, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: In vivo CAR-T; Oncolytic poxvirus
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell
• Other Study ID Numbers: 2026-0013

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