Hepatocellular Carcinoma
Conditions
Keywords
allogeneic γδT cells, hepatocellular carcinoma, adoptive immunotherapy
Brief summary
This study aims to evaluate the safety, tolerability and efficacy of ex-vivo expanded allogeneic γδT cells obtained from a blood-related donor of hepatocellular carcinoma patients.
Detailed description
This study is a single-center, non-randomized, open label, no control, prospective clinical trial to evaluate the safety, tolerability and efficacy of ex-vivo expanded allogeneic γδT cells from of a blood-related donor of Hepatocellular Carcinoma (HCC) Patients. This study will include the following sequential phases: sign informed consent, γδT cell pre-culture, screening and registration to the trial, apheresis, γδT cell preparation, treatments and follow-ups.
Interventions
BIOLOGICALEx-vivo expanded allogeneic γδT cells
Cells will be extracted from a healthy donor by apheresis, followed by ex-vivo expansion and activation. The ex-vivo expanded γδT cells from donors will be adoptively transfused.
Sponsors
Chinese Academy of Medical Sciences
Beijing GD Initiative Cell Therapy Technology Co., Ltd.
Beijing 302 Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Patient Inclusion Criteria: 1. Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study. 2. Age 18 years up to the age of 65 (≤65), gender unlimited. 3. Hepatocellular Carcinoma diagnosed according to the 2018 edition of the EASL guidelines. Patients should accept liver biopsy voluntarily and histopathologically diagnosed with HCC. 4. Interventional therapy (e.g. TACE), RFA or radiation therapy should be at least 2 weeks prior to γδT cell transfusion; surgical treatment should be at least 1 month prior to γδT cell transfusion. 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) 6. Eastern Cooperative Oncology Group (ECOG) Performance score≤2. 7. Life expectancy of at least 1 year. 8. Patients combined with HBV infection require antiviral treatment with nucleoside analogues; patients combined with HCV infection require direct-acting antiviral agent (DAA) treatment. 9. Male and female patients of reproductive potential must agree to use birth control during the study and for at least 30 days post study. Patient
Exclusion criteria
1. Patients combined with HAV, HEV, HIV or other infectious diseases. 2. Acute infections, gastrointestinal bleeding, etc. occurred within 30 days before screening. 3. Women who are pregnant (urine/blood pregnancy test positive) or lactating; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases. 4. Major organs dysfunction: * Peripheral blood: WBC\<1.0×109/L, PLT \<60×109/L, Hb \<86g/L; * Coagulation: INR\>2.3, PT\>18s; * Liver function: ALB\<28g/L, TBIL\>51mmol/L, ALT/AST\>5 times the upper limit of normal, CREA\>1.5 times the upper limit of normal. 5. Combined with other severe organic diseases or mental illnesses, including any uncontrolled clinically significant systematic 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 6 months prior to screening or during the study; 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. Donor Inclusion Criteria: 1. Sign informed consent form. 2. Age 18 years up to the age of 50 (≤50), gender unlimited. 3. Relative to patients (unrestricted to blood relationship). 4. Apheresis available. 5. PLT≥100×109/L with normal APTT or PT. Donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety evaluation: Incidence of Adverse events (AEs) | up to 48 weeks | Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). |
| Safety evaluation: Dose limited toxicity (DLTs) | up to 48 weeks | The incidence, characteristic and severity of DLTs will be recorded and assessed. |
| Safety evaluation: Maximum-tolerated dose (MTD) | up to 48 weeks | MTD or clinical recommended dose will be recorded and evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy evaluation: Quality of life by ECOG score | up to 48 weeks | The quality of life is assessed before and after the treatment by ECOG score . |
| Efficacy evaluation: Tumor markers | up to 48 weeks | Tumor markers in peripheral blood will be tested and assessed (e. g. AFP, AFP-L3). |
| Efficacy evaluation: γδT cells in peripheral blood | up to 48 weeks | Number and phenotype of γδT cells in peripheral blood will be assessed by flow cytometry. |
Countries
China
Outcome results
None listed