Refractory/Relapsed B-cell Lymphoma
Conditions
Keywords
Oncolytic poxvirus, In vivo CAR-T
Brief 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.
Interventions
BIOLOGICALCD19-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.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose limiting toxicity (DLTs) | Up to 28 days | To evaluate the safety, and tolerability, and determine the recommended dosage of the CD19-CAR novel oncolytic vaccinia virus |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CR) | Up to 2 years | To determine the anti-tumor effectivity of To determine the anti-tumor effectivity of the CD19-CAR novel oncolytic vaccinia virus |
| Progression free survival (PFS) | Up to 2 years | — |
| Duration of response (DOR) | Up to 2 years | — |
| Overall survival (OS) | Up to 2 years | — |
| Partial response rate (PR) | Up to 2 years | — |
| Overall response rate (ORR) | Up to 2 years | — |
Countries
China
Contacts
CONTACTWenbin Qian， Professor
Outcome results
None listed