A Clinical Study on the Safety and Efficacy of Allogeneic TCR-enhanced Vδ2 T Cell Injection in the Treatment of Patients With Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Adverse Event
研究概览
简要总结
The allogeneic TCR-enhanced Vδ2 T cell product is a novel genetically engineered cellular therapeutic. By engineering a specific BTN protein-binding moiety on its cell surface, this product harnesses the intrinsic tumoricidal potential of endogenous Vδ2 T cells and augments BTN protein recognition capability, thereby significantly boosting tumor cell killing potency. Notably, this engineered cell product exhibits no expression of co-stimulatory signaling domains and CD3ζ domains. This design circumvents T cell exhaustion triggered by overactivation and markedly enhances the in vivo persistence of therapeutic cells.
This is an open, prospective, open-label Phase I/II clinical trial designed to assess the safety and therapeutic efficacy of allogeneic TCR-enhanced Vδ2 T cell injection in patients with relapsed or refractory hematologic malignancies and advanced solid tumors.
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 18-75 (inclusive).
- •Expected survival time ≥ 3 months.
- •Meets current clinical diagnostic criteria with a confirmed diagnosis of a malignant hematologic tumor or solid tumor, and has failed standard therapy (for solid tumors, at least one evaluable lesion according to RECIST v1.1 is required).
- •Adequate bone marrow reserve and essentially normal liver and kidney function (laboratory tests must meet the following criteria prior to the first allogeneic TCR-enhanced Vδ2 T cell treatment):
- •Hematology: White Blood Cell Count (WBC) ≥ 2.5×10⁹/L, Lymphocyte Count (LY) ≥ 0.8×10⁹/L, Hemoglobin (Hb) ≥ 80 g/L, Platelets (PLT) ≥ 75×10⁹/L.
- •Liver: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; Total Bilirubin ≤ 3.0 × ULN.
- •Kidney: Serum Creatinine ≤ 1.5 × ULN.
- •Cardiac: Left Ventricular Ejection Fraction (LVEF) ≥ 50% as measured by echocardiogram.
- •Pulmonary: Normal oxygen saturation without supplemental oxygen.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-
- •A negative pregnancy test is required for women of childbearing potential. Both male and female subjects must agree to use effective contraception during the treatment period and for 1 year thereafter.
- •Able to understand the trial requirements and is willing to participate in the clinical study as required.
- •Voluntarily signs the informed consent form for the clinical trial.
排除标准
- •Known history of allergy, hypersensitivity, intolerance, or contraindication to allogeneic TCR-enhanced Vδ2 T cell or any components of the study drugs (including fludarabine, cyclophosphamide and albumin paclitaxel).
- •Continuous use of immunosuppressants within 1 month prior to allogeneic TCR-enhanced Vδ2 T cell infusion.
- •History of cerebrovascular accident or seizure within 6 months prior to signing the informed consent.
- •Symptomatic brain metastases.
- •Known psychiatric or substance abuse disorders that would compromise compliance with study requirements.
- •Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) with detectable Hepatitis B virus (HBV) DNA levels outside the normal reference range; positive for Hepatitis C virus (HCV) antibody with detectable HCV RNA; positive for Human Immunodeficiency Virus (HIV) antibody; positive for syphilis.
- •Severe cardiac disease, including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA Class ≥ III), and severe arrhythmia.
- •Active or uncontrolled infection requiring systemic therapy (except for mild urogenital and upper respiratory tract infections).
- •Has not recovered from acute toxic effects of prior therapy (i.e., persisting hematological or organ toxicity ≥ Grade 2 related to prior therapy, excluding abnormalities associated with the study disease and its history).
- •Diagnosed with immunodeficiency.
- •Active infection requiring systemic treatment.
- •Female subjects of childbearing potential planning pregnancy within 2 years after cell infusion; or male subjects whose partners are planning pregnancy within 2 years after cell infusion.
- •Participation in another investigational drug clinical study within 1 month prior to screening.
- •Last anti-tumor therapy administered less than 5 half-lives of the drug prior to planned allogeneic TCR-enhanced Vδ2 T cell infusion.
- •Any other condition deemed by the investigator to make the subject unsuitable for participation in this study.
结局指标
主要结局
Adverse Event
时间窗: 12 months
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after allogeneic TCR-enhanced Vδ2 T cells infusion. Among them, cytokine release syndrome (CRS), immune cell-associated neurotoxicity syndrome (ICANS) , graft-versushost disease (GVHD) are excluded . Other AEs were graded according to the regulatory agency's Medical Dictionary for Regulatory Activities (MedDRA) and common terminology criteria for adverse events (CTCAE) v5.0
DLTs
时间窗: 28 days after cell infusion
DLT was defined as allogeneic TCR-enhanced Vδ2 T cells-related events with onset within first 28 days following infusion
次要结局
- Overall Survival(OS)(12 months)
- Progression Free Survival (PFS)(12 months)
研究者
Han weidong
Director of the Division of Biotherapy, Department of Oncology
Chinese PLA General Hospital