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Prevention of Postoperative Recurrence of Hepatocellular Carcinoma by Blocking RAK Cells With Anti-TIM-3

Primary Purpose

Hepatocellular Carcinoma

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Autologous RAK cells
Sponsored by
Beijing Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 3) Patients diagnosed with HCC by histological examination; 4) According to China Liver Cancer Staging (CNLC) -- Guidelines for the Diagnosis and Treatment of primary liver Cancer of the National Health Commission of the People's Republic of China (2022 edition), patients with stage Ia and stage Ib ⅱA; 5) Undergoing radical resection of HCC; 6) For patients with hepatocellular carcinoma diagnosed by pathology after radical resection, the clinical and pathological characteristics meet one of the following conditions: A. tumor ≥5cm; B. Pathology suggested MVI (microvascular invasion); C. Pathology suggested satellite foci or sub-foci; D. Multiple tumors (number of tumors ≥2); E. AFP & GT; 20 mu g/L; F. Accompanied by hepatic capsule invasion; 7) ECOG score 0 or 1; Child-pugh liver function score A/B (≤7); 8) Neutrophil count ≥1.5×109/L, lymphocyte count ≥1.1×109/L, platelet count ≥80×109/L; Cardiac echocardiography showed that cardiac ejection fraction ≥50%, and 12-lead ECG showed no obvious abnormalities. Oxygen saturation ≥90%; Creatinine clearance rate CG formula ≥50 mL/min; ALT and AST 2.5 x ULN or less; Serum total bilirubin ≤1.5×ULN; 9) The estimated survival time is more than 6 months; 10) Fertile men or women with the possibility of becoming pregnant agree to use effective contraceptive methods (e.g., oral contraceptives, intrauterine devices, controlled sexual desire or barrier contraception combined with spermicide) during the trial and to continue contraception for 3 months after completion of treatment. Exclusion Criteria: 1) Pregnant or lactating women; 2) Previous systemic treatment: cytotoxic chemotherapy drugs within 3 months, targeted drugs within 2 months, interferon and/or interleukin-2 within 3 months, and leukocyte raising drugs within 2 weeks; Have been treated with drugs that target immune regulatory points; 3) Have used immunosuppressive agents (e.g., azathioprine, 6-mercaptopurine, cyclosporine, tisirolimus, everolimus, rapamycin, etc.); Long-term use of corticosteroids; 4) History of thromboembolism within the last 3 months or high risk of pulmonary embolism; 5) Previous use of DC-CIK or CIK cells, autologous RAK/LAK cells or other adoptive immunotherapy; 6) A history of other malignant diseases in the last 5 years (except cured skin cancer and carcinoma in situ of the cervix); 7) Uncontrolled epilepsy, central nervous system diseases, cerebrovascular accidents, or accompanied by other uncontrolled diseases; A history of mental disorders; 8) Clinically severe heart disease (NYHA) grade II or more congestive heart failure or severe arrhythmias requiring medical intervention; 9) Interstitial lung disease ≥2 degrees; 10) Accompanied by fever or infection; 11) Autoimmune diseases, including uncontrolled hypothyroidism and hyperthyroidism; 12) HIV/AIDS or syphilis antibody positive; 13) Allergic to any interferon and interleukin-2 preparations; 14) Participating in other trials within 4 weeks before enrollment; 15) Poor compliance or conditions deemed inappropriate for study inclusion by the investigator.

Sites / Locations

  • Beijing Hospital Center of BiotherapyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

anti-Tim3-blocked RAK cells

Unblocked RAK cells

Arm Description

ubjects were randomly assigned to receive anti-TIM-3 blocked RAK cells or untreated RAK cells.

ubjects were randomly assigned to receive anti-TIM-3 blocked RAK cells or untreated RAK cells.

Outcomes

Primary Outcome Measures

RFS
Recurrence-free survival (RFS) of postoperative TACE combined with TIM-3 block treated autologous RAK cells to prevent HCC recurrence

Secondary Outcome Measures

OS
Overall survival (OS) of postoperative TACE combined with TIM-3 blocked autologous RAK cells to prevent HCC recurrence

Full Information

First Posted
February 13, 2023
Last Updated
February 13, 2023
Sponsor
Beijing Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05738980
Brief Title
Prevention of Postoperative Recurrence of Hepatocellular Carcinoma by Blocking RAK Cells With Anti-TIM-3
Official Title
Prevention of Postoperative Recurrence of Hepatocellular Carcinoma by Blocking RAK Cells With Anti-TIM-3
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
To compare the safety and efficacy of unmodified RAK cells and anti-TIM-3 blocked autologous RAK cells in preventing postoperative recurrence of HCC by postoperative TACE therapy combined with immune cell therapy.
Detailed Description
Research process: Initial screening period (-7 to -1 days) • Sign an informed consent form; • Assign screening numbers; • Assessment of eligibility for initial screening. Day 0 (period 1) Reconfirm the inclusion and exclusion criteria; 50-60ml of anticoagulant peripheral blood was sampled; Treatment time: On (±2) days 15 and 16, Autologous RAK cells were reinfused for treatment (cycle 1). TACE was performed on day 28 (±7). Blood drawing from autologous RAK cells in the second cycle (week 10 ±7 days) The second cycle of autologous RAK cell transfusion treatment (12 weeks ±7 days after hepatocellular carcinoma surgery); Blood was drawn from autologous RAK cells in the third cycle (week 22 ±7 days); Reinfusion of autologous RAK cells in the third cycle (week 24 ±7 days); After completing 3 cycles of treatment, the patients were assessed by the investigator to be under control or remission of disease after treatment, and then they were followed up for treatment

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
88 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
anti-Tim3-blocked RAK cells
Arm Type
Experimental
Arm Description
ubjects were randomly assigned to receive anti-TIM-3 blocked RAK cells or untreated RAK cells.
Arm Title
Unblocked RAK cells
Arm Type
Experimental
Arm Description
ubjects were randomly assigned to receive anti-TIM-3 blocked RAK cells or untreated RAK cells.
Intervention Type
Biological
Intervention Name(s)
Autologous RAK cells
Intervention Description
Autologous RAK cells were treated by intravenous reinfusion
Primary Outcome Measure Information:
Title
RFS
Description
Recurrence-free survival (RFS) of postoperative TACE combined with TIM-3 block treated autologous RAK cells to prevent HCC recurrence
Time Frame
two years
Secondary Outcome Measure Information:
Title
OS
Description
Overall survival (OS) of postoperative TACE combined with TIM-3 blocked autologous RAK cells to prevent HCC recurrence
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 3) Patients diagnosed with HCC by histological examination; 4) According to China Liver Cancer Staging (CNLC) -- Guidelines for the Diagnosis and Treatment of primary liver Cancer of the National Health Commission of the People's Republic of China (2022 edition), patients with stage Ia and stage Ib ⅱA; 5) Undergoing radical resection of HCC; 6) For patients with hepatocellular carcinoma diagnosed by pathology after radical resection, the clinical and pathological characteristics meet one of the following conditions: A. tumor ≥5cm; B. Pathology suggested MVI (microvascular invasion); C. Pathology suggested satellite foci or sub-foci; D. Multiple tumors (number of tumors ≥2); E. AFP & GT; 20 mu g/L; F. Accompanied by hepatic capsule invasion; 7) ECOG score 0 or 1; Child-pugh liver function score A/B (≤7); 8) Neutrophil count ≥1.5×109/L, lymphocyte count ≥1.1×109/L, platelet count ≥80×109/L; Cardiac echocardiography showed that cardiac ejection fraction ≥50%, and 12-lead ECG showed no obvious abnormalities. Oxygen saturation ≥90%; Creatinine clearance rate CG formula ≥50 mL/min; ALT and AST 2.5 x ULN or less; Serum total bilirubin ≤1.5×ULN; 9) The estimated survival time is more than 6 months; 10) Fertile men or women with the possibility of becoming pregnant agree to use effective contraceptive methods (e.g., oral contraceptives, intrauterine devices, controlled sexual desire or barrier contraception combined with spermicide) during the trial and to continue contraception for 3 months after completion of treatment. Exclusion Criteria: 1) Pregnant or lactating women; 2) Previous systemic treatment: cytotoxic chemotherapy drugs within 3 months, targeted drugs within 2 months, interferon and/or interleukin-2 within 3 months, and leukocyte raising drugs within 2 weeks; Have been treated with drugs that target immune regulatory points; 3) Have used immunosuppressive agents (e.g., azathioprine, 6-mercaptopurine, cyclosporine, tisirolimus, everolimus, rapamycin, etc.); Long-term use of corticosteroids; 4) History of thromboembolism within the last 3 months or high risk of pulmonary embolism; 5) Previous use of DC-CIK or CIK cells, autologous RAK/LAK cells or other adoptive immunotherapy; 6) A history of other malignant diseases in the last 5 years (except cured skin cancer and carcinoma in situ of the cervix); 7) Uncontrolled epilepsy, central nervous system diseases, cerebrovascular accidents, or accompanied by other uncontrolled diseases; A history of mental disorders; 8) Clinically severe heart disease (NYHA) grade II or more congestive heart failure or severe arrhythmias requiring medical intervention; 9) Interstitial lung disease ≥2 degrees; 10) Accompanied by fever or infection; 11) Autoimmune diseases, including uncontrolled hypothyroidism and hyperthyroidism; 12) HIV/AIDS or syphilis antibody positive; 13) Allergic to any interferon and interleukin-2 preparations; 14) Participating in other trials within 4 weeks before enrollment; 15) Poor compliance or conditions deemed inappropriate for study inclusion by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caixia Liu, master
Phone
010-85133662
Email
liucxmm@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Ma, Doctor
Organizational Affiliation
Beijing Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Hospital Center of Biotherapy
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Beijing Hospital E Committee
Phone
85138105
Email
bjyyec@126.com

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
After the article was published

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Prevention of Postoperative Recurrence of Hepatocellular Carcinoma by Blocking RAK Cells With Anti-TIM-3

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