Immunotherapy of Advanced Hepatitis B Related Hepatocellular Carcinoma With γδT Cells

Phase 1

• Conditions: Hepatocellular Carcinoma
• Interventions: Biological: autologous γδT cells

• Registration Number: NCT04032392
• Lead Sponsor: Beijing 302 Hospital

Brief Summary

To evaluate the safety, tolerability and efficacy of autologous γδT cells in the treatment of advanced hepatitis B-related hepatocellular carcinoma.

Detailed Description

This is a single-centre, non-randomised, open label, no control, prospective clinical trial. The study will include the following sequential phases: sign informed consent, γδT cells pre-culture, fresh biopsy and screening, apheresis, γδT cells preparation, treatment and follow-up. The study will evaluate the safety, tolerability and efficacy of autologous γδT cells in patients with advanced hepatitis B related hepatocellular carcinoma (HCC) which are refractory to current treatment.

Stage I comprising a safety cohort of patients to identify a safe dose, Stage II comprising an expanded patient group for response signal identification, Stage III to confirm efficacy and safety.

Study Timeline

• Status Verified: 2019-07
• Study First Submitted: 2019-07-19
• Study Start: 2019-07-23
• Study First Submitted QC: 2019-07-23
• Last Update Submitted: 2019-07-23
• Study First Posted: 2019-07-25
• Last Update Posted: 2019-07-25
• Primary Completion: 2021-07-30
• Study Completion: 2022-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Patients should sign informed consent form voluntarily and comply with the requirements of this study.
2. Gender unlimited, age 18 to 70 years old.
3. Hepatocellular carcinoma histopathology proven by liver fresh biopsy.
4. According to the 2018 edition of the EASL guidelines for primary liver cancer, patients were diagnosed with advanced HBV-related hepatocellular carcinoma (BCLC stage B and C) by pathology and imaging; all patients required antiviral therapy with nucleoside analogues; other treatments (e.g. interventional therapy) at least 2 weeks prior to γδT cell infusion; patients can take the first- or second-line targeted drugs recommended by the guidelines, such as lenvatinib or sorafenib.
5. Liver function: Child-Pugh class A/B (5-9), Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
6. Expected survival ≥ 6 months.
7. Male and female of reproductive potential must agree to use birth control during the study and for at least 30 days post study.

Exclusion Criteria

1. Combine other viral liver diseases or other liver disease patients.
2. Acute infection, gastrointestinal bleeding, etc. occurred within 30 days before screening.
3. Pregnant or lactating women; patients after organ transplantation; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.
4. Dysfunction of major organs; patient white blood cell count <1.0×10e9/L, platelet count <60×10e9/L, hemoglobin <86g/L, prothrombin time (INR) >2.3, or prolonged clotting time >6 seconds, serum albumin <28g/L, total bilirubin >51mmol/L, ALT/AST >5 times the upper limit of normal, creatinine >1.5 times the upper limit of normal.
5. Combined with other serious organic diseases, mental illnesses, including any uncontrolled clinically significant systemic diseases such as urinary, circulatory, respiratory, neurological, psychiatric, digestive, endocrine and immune diseases.
6. Allergic constitution, history of allergies to blood products, known to be allergic to test substances.
7. Immunosuppressive or systemic cytotoxic drugs may require within six months prior to screening or during treatment; 6 months prior to screening accepted other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.; immunotherapy such as PD-1 and PD-L1 antibodies.
8. Patients currently participating in other clinical trials who may violate this treatment plan and observations.
9. Those who are unable or unwilling to provide informed consent or who are unable to comply with the research requirements.
10. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed: patients with any serious acute or chronic physical or mental illness, or laboratory abnormalities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Autologous γδT cells	autologous γδT cells	Subjects will receive 3 cycles of γδT cells treatments, at four-week intervals, each cycle has 2 infusions. Dose escalation subjects will receive 6 infusions with dose of γδT cells escalation from 1×10e9 to 6×10e9. Constant dose subjects will have single infusion intravenously at a target dose of 1\~2×10e9 γδT cells.

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	14 months	Overall survival is defined as the time from the day in which the patient is enrolled to the date on which the patient dies for any cause.
Incidence of adverse events (AEs) and serious adverse events (SAEs)	14 months	Incidence of adverse events (AEs) and serious adverse events (SAEs) of each patient will be recorded and analyzed.

Secondary Outcome Measures

Name	Time	Method
Patients-based Quality of Life Evaluation	14 months	According to the European Organization for Research and Treatment of Cancer (EORTC) quality of life of the core scale criteria QLQ-C30 to evaluate and compare patients life quality before and after treatment.
Objective Response Rate (ORR)	14 months	The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the response evaluation criteria in solid tumors (RECIST) guideline.

Trial Locations

Locations (2)

Beijing 302 Hospital of China; 🇨🇳 Beijing, Beijing, China

Beijing 302 hospital; 🇨🇳 Beijing, China