Exploratory Study of Oncolytic Vaccinia VIrus-Delivered Targeted CD19 In Vivo CAR-T/M Therapy for Refractory/Relapsed B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Incidence of dose limiting toxicity (DLTs)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age≥ 18 years old, up to 75 years old, male or female;
- •ECOG score 0-2;
- •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;
- •CD19 positive (immunohistochemistry or flow cytometry);
- •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;
- •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;
- •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);
- •Absolute peripheral blood neutrophil ≥ 1000/mm3, platelet ≥ 50,000/mm3;
- •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%;
- •Have sufficient understanding ability and voluntarily sign the informed consent form;
- •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;
- •Male patients must agree to practice effective birth control during the study and for 60 days after the last viral treatment.
排除标准
- •History of other tumors;
- •Vaccination with the smallpox vaccine within 3 months before or during the study treatment;
- •Receiving gene therapy or any type of oncolytic virus therapy within 3 months before the study treatment;
- •Other open wounds;
- •Active autoimmune diseases;
- •Uncontrolled active infections;
- •HIV infection, uncontrolled HBV, HCV, or syphilis infection;
- •Known central nervous system lymphoma;
- •Clinically significant heart disease;
- •Allergy to albumin or egg products;
- •History of organ transplantation or similar surgeries;
- •Need for systemic treatment for skin diseases;
- •History of severe systemic reactions or side effects after smallpox vaccination;
- •Known alcohol or viral dependence;
- •Pregnant or breastfeeding women.
研究组 & 干预措施
intratumoral or intravenous injection RGV005
Subjects will receive intratumoral injections of CD19-CAR oncolytic vaccinia virus (RGV005)
干预措施: CD19-CAR novel oncolytic vaccinia virus (Biological)
结局指标
主要结局
Incidence of dose limiting toxicity (DLTs)
时间窗: Up to 28 days
To evaluate the safety, and tolerability, and determine the recommended dosage of the CD19-CAR novel oncolytic vaccinia virus
次要结局
- Complete response rate (CR)(Up to 2 years)
- 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)