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

To study the safety and effectiveness of oncolytic Vaccinia VIrus-Delivered Targeted CD19In 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.

Recruiting
Refractory/Relapsed B-cell Lymphoma

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.

Eligibility Criteria

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.

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: 75 Years
Countries
China
Locations

The Second Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, China

Investigator: Wenbin Qian, Professor
Contact: +8613605801032
qianwb@zju.edu.cn

Contacts

Wenbin Qian, Professor
+8613605801032
qianwb@zju.edu.cn

Not Provided

Second Affiliated Hospital, School of Medicine, Zhejiang University
NCT Number
Keywords
Oncolytic poxvirus
In vivo CAR-T
MeSH Terms
Lymphoma, B-Cell