Adoptive Transfer of iNKT Cells for Treating Patients With Relapsed/Advanced HCC

Study Overview
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Brief Summary
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This study enrolls patients who have relapsed/advanced hepatocellular carcinoma (HCC, BCLC stage C). The HCC tumor relapsed or metastasized through the body after standard treatment or the patients cannot receive standard treatment under current conditions. This research study uses special immune system cells called iNKT cells, a new experimental treatment. The purpose of this study is to find the biggest dose of iNKT cells that is safe and tolerance, to see how long they last in the body, to learn the immunoresponse in the body, to learn the side effects are and to see if the iNKT cells will help people with relapsed/advanced hepatocellular carcinoma (HCC).

Official Title
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A Study of Adoptive Invariant Nature Killer T Cell Therapy for Relapsed/Advanced Hepatocellular Carcinoma (HCC)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: iNKT cells
* Drug: IL-2
* Drug: Tegafur


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years. Patients with hepatocellular carcinoma (BCLC, stage C) proved by histopathology or proved by CT or MRI imaging system, relapsed after previous therapy and no effective therapies known at this time. Life expectancy of ≥ 12 weeks. WBC>3.5×10^9/L, LYMPH> 0.8×10^9/L, Hb>85g/L, PLT>50×10^9/L, Cre<1.5×the upper limit of normal value. iNKT>10/mL in peripheral blood mononuclear cell (PBMC). Able to understand and sign the informed consent. Exclusion Criteria: Any uncontrolled systematic disease: hypertension, heart disease, and et al.; Portal vein tumor thrombus, central nervous system tumor metastasis, or combined with other tumors; Receiving radiochemotherapy, local therapy, or targeting drugs within 4 weeks prior to this treatment; Unstable immune systematic diseases or infectious diseases; Combined with AIDS or syphilis; Patients with history of stem cell or organ transplantation; Patients with allergic history to related drugs and immunotherapy; Patients with complications associated with liver diseases: moderate or severe pleural effusion, pericardial effusion, ascites, or gastrointestinal hemorrhage; Pregnant or lactating subjects; Unsuitable subjects considered by clinicians.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Three planned infusions for 18 patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous iNKT Cells + Tegafur +Interleukin-2(IL-2)<br>Autologous in vitro expanded iNKT cells in conjunction with IL-2 and along with lymphodepleting chemotherapy (Tegafur) will be administered to patients with advanced HCC. | Biological: iNKT cells<br>* Three different dosing schedules will be evaluated. Three patients will be evaluated on each dosing schedule. The following dose levels will be evaluated: Loading Dose 1: 3x10^7/m2 Loading Dose 2: 6x10^7/m2 Loading Dose 3: 9x10^7/m2 The doses are calculated according to the actual number of iNKT cells.<br>Drug: IL-2<br>* IL-2 will be given at a dose of 25,000 IU/kg/day for 5-14 days.<br>* Other names: Human recombinated Interleukin-2;Drug: Tegafur<br>* Tegafur will be given at a dose of 40 60 mg bis in die (BID) 2 weeks.<br>* Other names: Gimeracil and Oteracil Potassium Capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety] | Defined as signs/symptoms, laboratory toxicities, and clinical events that are possibly, likely, or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biological activity of infused iNKT cells | To assess the biological activity of infused in vitro expanded autologous iNKT cells in conjunction with IL-2. | 4 weeks |