Immunotherapy of Hepatocellular Carcinoma With Gamma Delta T Cells

Study Overview
=================
Brief Summary
-----------------
For most patients with hepatocellular carcinoma, surgery or other curative procedures are not possible and only palliative measures could be applied (chemoembolization, targeted drugs, best supportive cares, etc). In the ICAR study, increasing doses of a cell therapy product will be evaluated in patients in a palliative setting. All patients will have one hepatic intra-arterial injection of immunological cells (gamma-delta T lymphocytes) and will be evaluated for safety.

Official Title
-----------------
Immunotherapy of Hepatocellular Carcinoma by Hepatic Intra Arterial Injection of Autologous Gamma-delta T Lymphocytes: A Phase I Study

Conditions
-----------------
Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Other: T gamma delta lymphocytes


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult over 18 Hepatocellular carcinoma histologically proven, with at least one measurable tumor Non operable tumor Alfa foeto protein > 400 ng/ml Other treatments (surgery, chemoembolization) non indicated Chemoembolization non indicated due to good performance status (WHO 1) or to tumor volume Performance status WHO < 2 Life expectancy > 3 months Non inclusion Criteria: Extra hepatic metastases Severe hepatopathy (Child B or C) Virus B or C chronic hepatitis Chronic cardiac failure Uncontrolled severe infectious disease Other cancer, if not considered as cured Positive serology for HIV or HTLV Leucocytes < 3000/mm3 or neutrophils < 1500/mm3 Platelets < 80000/mm3 Serum creatinine > 110 µmol/L Bilirubin > 35 µmol/L AST, ALT, alkaline phosphatase > 5N Current immunosuppressive treatment Impossibility to comply with scheduled follow-up Anatomical situation not permitting the selective injection of the product of cell therapy Pregnant or breastfeeding woman, or not using adequate effective contraceptive method Exclusion Criterion: Insufficient number of gamma delta lymphocytes after expansion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Single hepatic intra arterial administration of 500 millions T gamma delta lymphocytes | Other: T gamma delta lymphocytes<br>* Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes<br>|
| Experimental: 2<br>Single hepatic intra arterial administration of 1000 millions T gamma delta lymphocytes | Other: T gamma delta lymphocytes<br>* Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes<br>|
| Experimental: 3<br>Single hepatic intra arterial administration of 2000 millions T gamma delta lymphocytes | Other: T gamma delta lymphocytes<br>* Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes<br>|
| Experimental: 4<br>Single hepatic intra arterial administration of 4000 millions T gamma delta lymphocytes | Other: T gamma delta lymphocytes<br>* Single hepatic intra arterial administration of increasing doses of T gamma delta lymphocytes<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset of: thrombosis of hepatic artery, grade 4 liver toxicity, or grade 3 or more allergic, neurological, dermatological, infectious, or respiratory reaction |  | Within 14 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset of clinical, biological signs or images evocative of lymphocyte-induced tumor cytotoxicity and/or of a persistence of gamma-delta T cells in peripheral blood. Tumor response will be evaluated with the RECIST criteria. |  | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cell therapy, T lymphocytes, hepatic intra-arterial injection