Immunotherapy of Advanced Hepatitis B Related Hepatocellular Carcinoma With γδT Cells

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

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: autologous γδT cells

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuanyuan Li, Dr; Phone Number: +86 01066933333; Email: lyy020818@sina.com

Study Locations

• China
  • Beijing, China, 100039
    • Beijing 302 Hospital
  • Beijing
    • Beijing, Beijing, China, 100039
      • Beijing 302 Hospital of China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: 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.	Biological: autologous γδT cells; Cells will be extracted by apheresis, followed by expanding and activating. The autologous γδT cells product will be adoptive transferred.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) and serious adverse events (SAEs)	Incidence of adverse events (AEs) and serious adverse events (SAEs) of each patient will be recorded and analyzed.	14 months
Overall survival (OS)	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.	14 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	14 months
Patients-based Quality of Life Evaluation	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.	14 months

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Fu-Sheng Wang, Dr, Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 23, 2019
• Primary Completion (Anticipated): July 30, 2021
• Study Completion (Anticipated): July 30, 2022

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): July 25, 2019
• Last Update Submitted That Met QC Criteria: July 23, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Hepatitis B; Hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Liver Neoplasms; Carcinoma; Hepatitis B; Hepatitis; Carcinoma, Hepatocellular
• Other Study ID Numbers: Beijing302-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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