Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2025-12-26 @ 1:08 AM
Study NCT ID:
NCT05673434
Status:
UNKNOWN
Last Update Posted:
2023-01-06
First Post:
2022-12-21
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Clinical Study on the Safety and Efficacy of CAR-T Therapy for the TM4SF1-positive Tumors of Digestive System
Sponsor:
Changhai Hospital
Organization:
Study Overview
Official Title:
A Clinical Study on the Safety and Efficacy of CAR-T Therapy for the TM4SF1-positive Tumors of Digestive System
Status:
UNKNOWN
Status Verified Date:
2022-12
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Transmembrane 4 L Six Family Member 1 (TM4SF1) is highly expressed in many tumors of digestive system .
The Chimeric Antigen Receptor T-cells (CAR-T) that target TM4SF1 has been generated in our good manufacturing practices (GMP) facility and the 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 positive tumors of digestive system. In this study, the safety, tolerance, and preliminary efficacy of CART-TM4SF1 cells will be examined in patients with refractory/recurrent advanced pancreatic cancer, colorectal cancer, gastric cancer or liver cancer.
Clinical and immunological responses will be evaluated about 30 days and last up to 2 years after CAR-T cell infusion.
The Chimeric Antigen Receptor T-cells (CAR-T) that target TM4SF1 has been generated in our good manufacturing practices (GMP) facility and the 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 positive tumors of digestive system. In this study, the safety, tolerance, and preliminary efficacy of CART-TM4SF1 cells will be examined in patients with refractory/recurrent advanced pancreatic cancer, colorectal cancer, gastric cancer or liver cancer.
Clinical and immunological responses will be evaluated about 30 days and last up to 2 years after CAR-T cell infusion.
Detailed Description:
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.The investigators have developed novel TM4SF1-targeting CAR T-cells (CART-TM4SF1 cells) for the treatment of digestive system tumors.
These engineered T-cells can target and kill the TM4SF1-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 for digestive system tumors in patients.
Objectives:
Primary objectives:
1. To determine the safety/tolerance dosages and adverse effects of CART-TM4SF1 cells cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
2. To preliminarily evaluate the efficacy of CART-TM4SF1 cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
Secondary objectives:
1. To determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of CART-TM4SF1 cells in humans.
2. To evaluate the overall survival (OS) and tumor regression after treatment.
3. To assess the life quality of patients
Study population:
The study population includes 12-24 patients with refractory/recurrent advanced digestive system tumors with positive expression of TM4SF1. The subjects will receive four incremental doses (3-6 subjects in each dose group), as well as safety and preliminary efficacy evaluation.
Design:
* This is a single-center open-label clinical study.
* Recruit patients with refractory/recurrent digestive system tumors, with written consent for this study. Perform biopsy to determine the expression of TM4SF1 of the tumor with immuno-histochemistry (IHC).
* Collect peripheral blood mononuclear cell (PBMC) from the patients, isolate and activate the T cells and transfect them with TM4SF1 targeting CAR, expand the transfected T cells as needed, assess the quality and antitumor activity of the CAR-T products in vitro and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed.
* Clinical and immunological responses will be evaluated closely in about 30 days and last up to 2 years after back-transfusion.
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.The investigators have developed novel TM4SF1-targeting CAR T-cells (CART-TM4SF1 cells) for the treatment of digestive system tumors.
These engineered T-cells can target and kill the TM4SF1-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 for digestive system tumors in patients.
Objectives:
Primary objectives:
1. To determine the safety/tolerance dosages and adverse effects of CART-TM4SF1 cells cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
2. To preliminarily evaluate the efficacy of CART-TM4SF1 cells in the treatment of TM4SF1-positive recurrent/refractory advanced tumors of digestive system.
Secondary objectives:
1. To determine the pharmacokinetic (PK)/pharmacodynamic (PD) characteristics of CART-TM4SF1 cells in humans.
2. To evaluate the overall survival (OS) and tumor regression after treatment.
3. To assess the life quality of patients
Study population:
The study population includes 12-24 patients with refractory/recurrent advanced digestive system tumors with positive expression of TM4SF1. The subjects will receive four incremental doses (3-6 subjects in each dose group), as well as safety and preliminary efficacy evaluation.
Design:
* This is a single-center open-label clinical study.
* Recruit patients with refractory/recurrent digestive system tumors, with written consent for this study. Perform biopsy to determine the expression of TM4SF1 of the tumor with immuno-histochemistry (IHC).
* Collect peripheral blood mononuclear cell (PBMC) from the patients, isolate and activate the T cells and transfect them with TM4SF1 targeting CAR, expand the transfected T cells as needed, assess the quality and antitumor activity of the CAR-T products in vitro and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed.
* Clinical and immunological responses will be evaluated closely in about 30 days and last up to 2 years after back-transfusion.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: