Safety and Efficacy of Autologous Tumor-infiltrating Lymphocytes Therapy in Patients With Hepatocellular Carcinoma

This is a Phase 1, open label clinical trial of tumor-infiltrating lymphocytes for the treatment of patients with hepatocellular carcinoma. The purpose of this study is to assess the safety of tumor-infiltrating lymphocytes therapy in patients with hepatocellular carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: Autologous Tumor-infiltrating Lymphocytes

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Junliang Fu, PhD, MD; Phone Number: 86-10-66933214; Email: fjunliang@163.com
• Study Contact Backup: Name: Fu-Sheng Wang, PhD, MD; Phone Number: 86-10-66933328; Email: fswang302@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • The fifth medical center of PLA
    • Contact: Junliang Fu, PhD, MD; Phone Number: 86-10-66933214; Email: fjunliang@163.com
    • Contact: Fu-Sheng Wang, PhD, MD; Phone Number: 86-10-66933328; Email: fswang302@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 to 70 years;
2. Diagnosis of HCC with BCLC stage B/C;
3. Anticipated survival time is longer than 3 months;
4. Liver function grade Child-Pugh A or B, without hepatic encephalopathy;
5. Left ventricular ejection fraction (LVEF) ≥ 50%;
6. ECOG physical status 0-2;
7. Laboratory tests at baseline meet the following: Absolute neutrophil count >1.0 x 109/L; Absolute neutrophil count >1.0 x 109/L; White blood cell count > 2.0 x 109/L; Platelet count > 60 x 109/L; Hgb > 8.0 g/dL; ALT and AST ≤ 5 times the upper limit of normal (ULN), Serum total bilirubin (TBiL) ≤ 51 mmol/L, or < 3 times the ULN.
8. Female subjects of childbearing potential must take acceptable measures to minimize the likelihood of pregnancy during the trial. Female subjects of childbearing potential must have a negative serum or urine pregnancy result within 48 hours prior to treatment;
9. Able to receive treatment and follow-up, including the need for the subject to receive treatment at the enrollment center.

Exclusion Criteria:

1. Pregnant or breastfeeding women;
2. WIth HIV/AIDS infection;
3. Active infection with a temperature >38.3°C prior to study treatment and have been treated with antibiotics within 2 weeks prior to enrollment;
4. Presence of the following pre-existing or concomitant diseases: Prior diagnosis of a severe autoimmune disease requiring systemic immunosuppression (steroids) for a prolonged period of time (more than 2 months), or immune-mediated symptomatic disease; Prior diagnosis of autoimmune-induced motor neuron disease; Prior toxic epidermal necrolysis release; Subjects with any psychiatric condition, including dementia, altered mental status, which may interfere with treatment in this study; Subjects with other malignancies in the previous 5 years; Subjects with heart failure ≥ grade 2 (NYHA) or hypertension uncontrolled by standard therapy; Subjects with unstable or active peptic ulcer or gastrointestinal bleeding; Subjects with serious uncontrollable disease, as determined by the study, that may interfere with treatment in this study;
5. Subjects undergoing treatment with systemic steroids;
6. Subjects who have previously used immune cell therapy (CIK, DC, DC-CIK, LAK therapy) and are less than 28 days from the end of treatment to screening;
7. Subjects who are allergic to cell therapy products or related drugs;
8. Subjects who have previously received an organ transplant or are planning to receive an organ transplant;
9. Subjects requiring anticoagulant therapy (warfarin or heparin);
10. Subjects who are judged by the investigator to be unsuitable for participation in this study due to other conditions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tumor-infiltrating Lymphocytes Therapy; Autologous Tumor-infiltrating Lymphocytes Therapy, 2.0*10^7/Kg, single intravenous infusion.	Procedure: Autologous Tumor-infiltrating Lymphocytes; Autologous Tumor-infiltrating Lymphocytes, 2.0*10^7/Kg, single intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Safety and Tolerability of Autologous Tumor-infiltrating Lymphocytes Therapy	day0, day3, week1, week2, week4, week12, week24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Total Bilirubin (TBIL, mg/dL)	Total bilirubin refers to the concentration of bilirubin in a patient's blood sample, which is automatically measured by the laboratories in accordance with standard operating procedures.	day0, day3, week1, week2, week4, week12, week24
Child-Turcotte-Pugh(CTP) score	CTP score is currently the most commonly used model to evaluate liver reserve function and prognosis in patients with cirrhosis. This model evaluates liver function based on HE grade, degree of abdominal fluid accumulation, bilirubin (TBiL), albumin (Alb) and prothrombin time (PT). The score ranges from 0 to 15, with the higher the score, the worse the prognosis.	day0, day3, week1, week2, week4, week12, week24
Quality of life of patients	Quality of life assessed by Functional Assessment of Cancer Therapy - Hepatobiliary Symptom Index， which has a score ranges 0-32, a higher score indicates better quality of life.	day0, day3, week1, week2, week4, week12, week24

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Investigators: Principal Investigator: Junliang Fu, PhD, MD, The fifth medical center of PLA

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: April 26, 2024
• First Submitted That Met QC Criteria: June 14, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2024
• Last Update Submitted That Met QC Criteria: August 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Tumor-infiltrating Lymphocytes
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: KY-2024-3-48-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No