Immunotherapy of Advanced Hepatitis B Related Hepatocellular Carcinoma With γδT Cells

NCT ID: NCT04032392

Last Updated: 2019-07-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-23
• Study Completion Date: 2022-07-30

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

autologous γδT cells

Intervention Type: BIOLOGICAL

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

Interventions

autologous γδT cells

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fu-Sheng Wang, Dr

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital

Locations

Beijing 302 Hospital of China

Beijing, Beijing Municipality, China

Beijing 302 hospital

Beijing, , China

Countries

China

Central Contacts

Yuanyuan Li, Dr

Role: CONTACT

lyy020818@sina.com

+86 01066933333

Facility Contacts

Fu-Sheng Wang, MD

Role: primary

fswang302@163.com

01066933328

Yuanyuan Li, Dr

Role: primary

lyy020818@sina.com

+8601066933333

Other Identifiers

Beijing302-013

Identifier Type: -

Identifier Source: org_study_id