Immunotherapy Using Pluripotent Killer-Programmed Cell Death 1 (PIK-PD-1) Cells for the Treatment of Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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Objectives: The purpose of this study is to evaluate the safety and efficacy of PIK-PD-1 Cells in the treatment of advanced Hepatocellular Carcinoma. Methods: This study designs a novel therapy using PIK-PD-1 cells. 40 patients with advanced Hepatocellular Carcinoma will be enrolled. They are randomly divided into dendritic cell-precision multiple antigen T cells (DC-PMAT) group and PIK-PD-1 cells group. Both DC-PMAT treatment and PIK-PD-1 cells treatment will be performed every 3 weeks with a total of three periods. The mail clinical indicators are Progression-Free-Survival and Overall Survival.

Detailed Description
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A total of 40 patients may be enrolled over a period of 1-2 years.

Official Title
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A Clinical Study of Adoptive Cellular Immunotherapy Using Pluripotent Killer T Cells Expressing Antibodies for Programmed Death 1 (PD-1) in Treating Patients With Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: PIK-PD-1 cells
* Biological: DC-PMAT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 20 70 years old, male or female; 2. Barcelona Clinic Liver Cancer(BCLC) C stage; no indication for operation, local treatment (Transcatheter Arterial Chemoembolization (TACE), percutaneous icro wave coagulation therapy (PMCT), percutaneous ethanol injection therapy (PEIT)) and radiation therapy; unable or unwilling to receive sorafenib therapy; 3.Child-Pugh score ≤ 9; 4.Eastern Cooperative Oncology Group (ECOG) score ≤ 2; 5.Life expectancy>3 months; 6. white blood cell (WBC) > 3 x 10*9/L, Neutrophils > 1 x 10*9/L, lymphocyte > 1 x 10*9/L, hemoglobin ≥8.5g/dl, Platelet ≥50×109/L, prothrombin time (PT) no more than 3 seconds, Cr and blood urea nitrogen (BUN) less than 3 times of the normal level; 7. Adequate venous access, blood cell production without other taboos; 8. Signed informed consent. Exclusion Criteria: 1. Immunosuppressive therapy needed with autoimmune disease or organ transplantation history； 2. HIV/Syphilis infection; 3. Positive blood culture or imaging evidence infection; 4. Other drugs, gene therapy, biological, chemotherapy or radiation therapy were used within 1 months. 5. The history of allergic reactions in cell therapy or cytokine. 6. PD-1 antibodies have been used before, or allergies due to PD-1 antibody drugs. 7. History of interstitial lung disease. 8. History of esophagus varicosis rupture haemorrhage. 9. Other serious diseases:the heart,lung, kidney, digestive, nervous, mental disorders, immune regulatory diseases, metabolic diseases, infectious diseases, Etc. 10. Pregnant, lactating women, or pregnancy planned at the following 2 years. 11. Without signed informed consent. 12. Other researchers considered ones unsuitable for inclusion.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PIK-PD-1 cells<br>PIK-PD-1 cells treatment will be performed every 3 weeks with a total of three periods. | Biological: PIK-PD-1 cells<br>* DC cell suspension (1×10*7 DC+ physiological saline + 0.25% human serum albumin) 1ml for each infusion, subcutaneous injection for each infusion 3 cycles, each cycle received two infusions on day 19, 20; 40, 41; 61, 62. PIK-PD-1 cell suspension (1-6×10*9 PIK-PD-1 + physiological saline + 0.25% human serum albumin) 300ml for each infusion, IV (in the vein) for each infusion 3 cycles, each cycle received one infusions on day 21, 42, 63.<br>|
| Active Comparator: DC-PMAT<br>DC-PMAT cells treatment will be performed every 3 weeks with a total of three periods. | Biological: DC-PMAT<br>* DC cell suspension (1×10*7 DC+ physiological saline + 0.25% human serum albumin) 1ml for each infusion, subcutaneous injection for each infusion 3 cycles, each cycle received two infusions on day 19, 20; 40, 41; 61, 62. PMAT cell suspension (1-6×10*9 PMAT + physiological saline + 0.25% human serum albumin) 300ml for each infusion, IV (in the vein) for each infusion 3 cycles, each cycle received one infusions on day 21, 42, 63.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2 yeas | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress-free survival |  | 2 yeas | 
| Quality of life | Quality of life core questionnaire will be used. | 2 yeas | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PIK-PD-1 Cells, dendritic cell-precision multiple antigen T cells, advanced hepatocellular carcinoma