NCT04151186Unknown不适用
A Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T-cell Therapy for the TM4SF1- and EpCAM-positive Recurrent/Refractory Solid Tumors
suhaichuan0 个研究点目标入组 72 人开始时间: 2019年11月20日最近更新:
适应症
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 72
- 主要终点
- Safety assessed by Incidence of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
- Transmembrane 4 L Six Family Member 1 (TM4SF1) and Epithelial cell adhesion molecule (EpCAM) are both highly expressed in many epithelial-derived solid tumors.
- The Chimeric Antigen Receptor T-cells (CAR-T) that target TM4SF1 or EpCAM have been generated respectively in our good manufacturing practices (GMP) facility and their anti-tumor effects have been demonstrated in multiple in vitro and in vivo studies.
- Clinical studies are proposed here to evaluate the anti-tumor activity of these cell therapy products for treatment of patients with TM4SF1 or EpCAM positive tumors. In this study, the safety, tolerance, and preliminary efficacy of CART-TM4SF1 and CART-EpCAM cells will be examined inpatients with refractory/recurrent advanced pancreatic cancer, colorectal cancer, gastric cancer or lung cancer. And 9 patients for each cancer will be evaluated.
- Clinical and immunological responses will be evaluated about 30 days and last up to 2 years after CAR-T cell infusion.
详细描述
Background:
- While great progress has been made in CAR T-cell therapy for the treatment of hematologic malignancies, its use in solid tumors is still at the exploratory stage.
- Transmembrane 4 L Six Family Member 1 (TM4SF1) protein mediates signal transduction events that play a role in the regulation of cell development, activation, growth and motility. It is a cell surface antigen and is highly expressed in different carcinomas. Epithelial cell adhesion molecule (EpCAM),is a transmembrane glycoprotein of 40 kilodaltons (kDa). EpCAM is highly expressed in many epithelial-derived tumors, such as colon, stomach, pancreas, lungs, ovaries and breasts. Recently, EpCAM has been identified as the surface marker of circulating tumor cells (CTCs) and cancer stem cells (CSCs).
- The investigators have developed novel TM4SF1-targeting CAR T-cells (CART-TM4SF1 cells) and EpCAM-targeting CAR T-cells (CART-EpCAM cells) for solid tumor treatment. These engineered T-cells can target and kill the TM4SF1- or EpCAM-positive tumor cells in vitro or in mice. Both of the CAR molecules contain a safety switch based on epidermal growth factor receptor (EGFR) to ensure the safety.
- The investigators propose to investigate the feasibility, safety, and efficacy of CART-TM4SF1 cells and CART-EpCAM cells for solid cancers in patients.
Objectives:
Primary objectives:
- To determine the safety/tolerance dosages and adverse effects of CART-TM4SF1 cells or CART-EpCAM cells in the treatment of TM4SF1- or EpCAM-positive recurrent/refractory advanced solid tumors.
- To preliminarily evaluate the efficacy of CART-TM4SF1 cells and CART-EpCAM cells in the treatment of TM4SF1- and EpCAM-positive recurrent/refractory 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
- •Aged≥18 years old and ≤75 years old when signing the informed consent; regardless of gender;
- •Body weight>40kg;
- •Pathologically confirmed as pancreatic cancer, colorectal cancer, gastric cancer or lung cancer;
- •Recurrent/refractory solid tumors unresponsive to the current standard treatment;
- •At least one measurable lesion according to the RECIST 1.1 criteria, that is, the long diameter of the non-lymph-node lesion≥10 mm, or the short diameter of the lymph node lesion ≥15 mm on CT or MRI cross-sectional imaging; the longest axis of the measurable lesion≥10 mm on CT scan (slice thickness≤5 mm in CT scan);
- •Acceptable hemopoietic ability: absolute neutrophil count (ANC) >1.5×10^9/L, platelet count >1.0×10^11/L, hemoglobin (HGB) >90g/L (no blood transfusion within two weeks), absolute lymphocyte count (ALC )>500×10^9/L;
- •Acceptable liver and kidney functions: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ULN in subjects without liver metastases and ≤3.5 upper limit of normal (ULN) in those with liver metastases; bilirubin≤1.5 ULN (excluding hyperbilirubinemia or non-liver-derived hyperbilirubinemia); creatinine ≤1.5 ULN and creatinine clearance rate≥40 mL/min;
- •prothrombin time (PT)/international normalized ratio (INR) <1.5 ULN and partial thromboplastin time (PTT)/activated partial thromboplastin time (APTT) <1.5 ULN;
- •Positive for TM4SF1 or EpCAM expression (expression≥25%), with three classifications; (1) Recurrent or existing lesions at the primary site with tumor tissue samples collected within 1 year, which are positive for TM4SF1 or EpCAM by immunohistochemistry; (2) New metastatic lesions at the non-primary sites, which are positive for TM4SF1 or EpCAM by immunohistochemistry; (3) Remaining tumor lesions at the primary site with tumor tissue samples collected more than 1 year ago, and the lesions are positive for TM4SF1 or EpCAM by immunohistochemistry based on re-biopsy.
- •Women of child-bearing age (15-49 years old) must be negative for pregnancy test at 7 days before initiation of the treatment.
- •Eastern Cooperative Oncology Group (ECOG) scores≤
- •Expected survival no less than 12 weeks.
排除标准
- •History of any radiotherapy and chemotherapy within 4 weeks before a single blood collection;
- •History of any anti-programmed cell death protein 1 (PD1) and anti-Programmed cell death 1 ligand 1 (PD-L1) treatments within 12 weeks before a single blood collection;
- •History of organ transplantation;
- •Pregnancy or lactation;
- •Uncontrolled infectious diseases, such as baseline hepatitis B virus (HBV) DNA≥2000 IU/ml, positive for anti-human immunodeficiency virus （HIV） antibody and hepatitis C virus (HCV)-RNA;
- •Other active infection with clinical significance;
- •History of other active malignancies in the past 5 years, excluding basal or squamous skin carcinoma, superficial bladder cancer, and breast cancer in situ which have completely healed and require no follow-up treatment;
- •Serious autoimmune diseases or immunodeficiency disease, including those with confirmed severe autoimmune diseases and requiring long-term use (over 2 months) of systemic immunosuppressants (steroids) or having immune-mediated symptomatic diseases, such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE) and autoimmune vasculitis (eg., Wegener's granulomatosis);
- •Allergic diathesis and allergic to immunotherapy or relevant drugs;
- •Organ failure; Heart: Grade III and IV ; or with hypertension uncontrolled by the standard treatment, history of myocarditis or myocardial infarction within 1 year; Liver: Class C according to the Child-Turcottei-Pugh System (CTP); Kidneys: Kidney failure and uremic syndrome; Lungs: Serious symptoms of respiratory failure; Brain: Disturbance of consciousness;
- •Active bleeding, and thrombotic diseases requiring treatment;
- •Uncontrollable pleural and peritoneal effusion requiring clinical treatment or intervention;
- •T-cell cancers, such as T-cell lymphoma;
- •Current on systemic steroid or steroid inhalers;
- •Any mental diseases, including dementia and changes in mental status that may influence the understanding about the informed consent and questionnaire;
- •Participating in other clinical trials in the past 30 days;
- •Judged as serious uncontrollable diseases by the researchers, or other conditions that may interfere with the treatment and therefore being ineligible.
结局指标
主要结局
Safety assessed by Incidence of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 2 years
1. After CAR-T cell infusion,the investigators will observe the potential adverse events related to the CAR-T cells infusion such as high fever, kidney failure and so on. 2. Adverse events are coded according to MedDRA 22.0. List total number of AEs and SAEs; Number of subjects with different types of AEs and SAEs, case-times and incidence.AEs and SAEs are graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTC AE version 5.0).
次要结局
- CAR-T cell testing(2 years)
- Overall response rate (ORR)(2 years)
研究者
suhaichuan
professor
Tang-Du Hospital
相似试验
尚未招募
不适用
A Clinical Study on the Safety and Efficacy of CAR-T Therapy for the TM4SF1-positive Tumors of Digestive SystemDigestive TumorNCT05673434Changhai Hospital24
终止
2 期
Clinical Study of CAR-T Cell Therapy Following ASCT for R/R B-cell Non-Hodgkin's LymphomaLymphoma, B-CellAutologous Stem Cell TransplantationNCT06381830The First Affiliated Hospital of Soochow University8
Unknown
1 期
Study of CDK4/6 Inhibitor Combined With PD-L1 Monoclonal Antibody in the Treatment of PD-1/PD-L1 Resistance and Abnormal Cell Cycle Digestive System TumorsDigestive System TumorsNCT05139082Peking University60
已完成
1 期
CIML NK Cell in Head & Neck CancerSquamous Cell Carcinoma of the Head and NeckRecurrent Head and Neck Squamous Cell CarcinomaNCT04290546Dana-Farber Cancer Institute11
招募中
2 期
Chimeric Antigen Receptor Modified T Cells Targeting BCMA for the Treatment of Relapsed/Refractory Multiple MyelomaRelapsed/RefractoryMultiple MyelomaNCT06581640The First Affiliated Hospital of Xiamen University5