A Clinical Study on the Safety and Efficacy of CAR-T Therapy for the TM4SF1-positive Tumors of Digestive System

NCT05673434 | Unknown

• 1 other identifier: CART-TM4SF1-01
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Digestive Tumor

Keywords

Neoplasms

Outcome Measures

Primary Outcomes (1)

• Safety assessed by Incidence of Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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. 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).

  2 years

Secondary Outcomes (2)

• Overall response rate (ORR)

  2 years

• CAR-T cell testing

  2 years

Study Arms (1)

Experimental: TM4SF1 positive CAR-T cells for digestive tumors

EXPERIMENTAL

The present study is proposed to study advanced malignant digestive tumors in adults, and the four escalating doses, namely, 0.5\~1.0.,1.0\~2.0,2.0\~3.0 and 3.0\~10.0 (×10 \^6/kg), will be given. Intervention: Biological: TM4SF1-positive chimeric antigen receptor T-cell therapy

Biological: TM4SF1-positive chimeric antigen receptor T-cell therapy

Interventions

TM4SF1-positive chimeric antigen receptor T-cell therapy BIOLOGICAL

Specification: 50mL/bag. Storage: The prepared CAR T-cells are cryopreserved in a preserving medium . This product is manufactured under the current good manufacture practices (cGMP) conditions, with restrictions on chemical components, free from animal- or human-derived components and confirming to the United States Pharmacopeia (USP)\<71\> and \<85\> regulations. Preservation: The frozen CAR T-cells are preserved in the liquid nitrogen transfer tank. Usage: The frozen CAR T-cells are preserved at low temperature and transferred to the bedside. The cells are thawed by 36 degrees centigrade to 38 degrees centigrade. water bath. The frozen cells are gently massaged until complete thawing. Then they are transfused back to the patients intravenously. The transfusion will be finished within 10-20 min.

Experimental: TM4SF1 positive CAR-T cells for digestive tumors

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The age at the time of signing the informed consent is ≥ 18 years old and ≤ 75 years old, regardless of gender;
• BMI ≥ 18.5 (weight (kg)/height (m ²）)；
• The physical condition score of the Eastern Cooperative Oncology Group (ECOG) is ≤ 2 points;
• The estimated survival time is not less than 12 weeks;
• Patients confirmed by histology or cytology, who progress after standard treatment failure, or cannot accept/fail patients with advanced solid tumors with standard treatment, such as gastric cancer, colorectal cancer, pancreatic cancer and other digestive system tumors.
• According to RECIST 1.1 standard, there is at least one measurable lesion, that is, according to CT or MRI cross section on imaging, the long diameter of non lymph node lesions ≥ 10 mm, or the short diameter of lymph node lesions ≥ 15 mm; measurable disease CT scanning of the longest axis of the focus ≥ 10 mm (CT scanning slice thickness ≤ 5 mm), and the measurable part should not be accepted local treatment such as radiotherapy (for lesions located in the previous radiotherapy area, if progress is confirmed, it is also optional target lesion);
• It has suitable organs and hematopoietic function (It is not allowed to use any blood components, cytokines, leukemic agents, platelet promoting agents and human albumin preparations within 14 days before screening), according to the following laboratory tests:
• Color Doppler echocardiography showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥ 50%, and no large amount of pericardial effusion
• Finger oxygen saturation\>93%；
• Neutrophil (ANC) ≥ 1.5 × 10 9 /L；
• Platelet count≥75×10 9 /L；
• Hemoglobin (HGB)\>90g/L；
• Absolute lymphocyte count (ALC)≥0.8×10 9 /L；
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal value (ULN) in patients without liver metastasis and ≤ 3.5 times ULN in patients with liver metastasis;
• total bilirubin≤1.5 times ULN；

You may not qualify if:

• Subjects with allergic constitution and allergy to immunotherapy or related drugs；
• Adverse reactions of previous treatment failed to recover to CTCAE v5.0 grade ≤ 1 ；
• Patients expected to have major surgery during the study period, including the screening period;；
• Patients with severe autoimmune diseases requiring long-term (more than 2 months) systemic immunosuppressive therapy;；
• Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident, transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure（≥ NYHA Class III）, severe arrhythmia with poor drug control, liver, kidney or metabolic disease, and hypertension beyond control through standard treatment
• Known or suspected brain metastasis, including central nervous system and spinal cord compression or meningeal metastasis patient；
• Other active malignant tumors in the past 5 years
• Patients with active bleeding and thrombotic disease requiring treatment;
• Patients with pleural and peritoneal effusion who cannot be controlled and need clinical treatment or intervention；
• Patients who used corticosteroid hormones (prednisone ≥ 20mg/day or other corticosteroid hormones with equivalent dose) and other immunosuppressants with pharmacological dose 7 days before cell collection and 5 days before cell reinfusion in this study；
• Alcohol dependent persons or those who have a history of drug abuse or drug abuse in the past one year；
• Subjects with any mental illness that may affect the understanding of informed consent；
• Patients with acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; Patients with human immunodeficiency virus (HIV) antibody positive; Patients with treponema pallidum antibody test positive

Sponsors & Collaborators

• Changhai Hospital: lead
• Shanghai Ultra-T Immune Therapeutics Co. LTD: collaborator

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MeSH Terms

Conditions

Digestive System Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Digestive System Diseases

Central Study Contacts

Xianbao Zhan, professor

CONTACT

+86 13501850100; zhanxianbao@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 6, 2023
• Study Start: January 30, 2023
• Primary Completion: July 30, 2024
• Study Completion: January 30, 2025
• Last Updated: January 6, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share