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

NCT ID: NCT05738980

Last Updated: 2023-02-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2026-12-31

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.

1. Day 0 (period 1)

• Reconfirm the inclusion and exclusion criteria;
• 50-60ml of anticoagulant peripheral blood was sampled;

Treatment time:

2. On (±2) days 15 and 16, Autologous RAK cells were reinfused for treatment (cycle 1).

3. TACE was performed on day 28 (±7).

4. Blood drawing from autologous RAK cells in the second cycle (week 10 ±7 days)

5. The second cycle of autologous RAK cell transfusion treatment (12 weeks ±7 days after hepatocellular carcinoma surgery);

6. Blood was drawn from autologous RAK cells in the third cycle (week 22 ±7 days);

7. 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

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

anti-Tim3-blocked RAK cells

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

Group Type: EXPERIMENTAL

Autologous RAK cells

Intervention Type: BIOLOGICAL

Autologous RAK cells were treated by intravenous reinfusion

Unblocked RAK cells

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

Group Type: EXPERIMENTAL

Autologous RAK cells

Intervention Type: BIOLOGICAL

Autologous RAK cells were treated by intravenous reinfusion

Interventions

Autologous RAK cells

Autologous RAK cells were treated by intravenous reinfusion

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jie Ma, Doctor

Role: PRINCIPAL_INVESTIGATOR

Beijing Hospital

Locations

Beijing Hospital Center of Biotherapy

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Caixia Liu, master

Role: CONTACT

liucxmm@163.com

010-85133662

Facility Contacts

Beijing Hospital E Committee

Role: primary

bjyyec@126.com

85138105

Other Identifiers

BJH Biotherapy Center

Identifier Type: -

Identifier Source: org_study_id