Safety Study of NK Cells From Sibship to Treat the Recurrence of HCC After Liver Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to explore the safety of NK cells from Sibship in patients with recurrent hepatocellular carcinoma after liver transplantation.

Detailed Description
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Hepatocellular carcinoma (HCC) is one of the indications for the liver transplantation. With the advancement of liver transplantation associated science and technology, the recurrence of tumor posttransplantation has become the principal contradiction to worsen the prognosis and therefore the prevention of recurrence of HCC is the key to improve the efficacy of liver transplantation. Adoptive cellular immunotherapy has been applied in various malignant tumors including HCC and has obtained significant effects. But for patients with liver transplant in immunosuppressed states, to successfully apply the immune cells to prevent and treat HCC relapse after liver transplantation must balance immunosuppression and anti-tumor immunity. It is necessary to consider the safety of adoptive cellular immunotherapy,and it is also necessary to consider the effectiveness of treatment that the immune cells in the immunosuppression state can exert anti-tumor effects. Natural killer cells (NK cells) have MHC-unrestricted killing effect on malignant tumor cells and are not major mediating cells for GVHD, and might be an optimum choice to meet the above requirements. Patients with confirmed recurrence of hepatocellular carcinoma after liver transplantation at the Third Affiliated Hospital of Sun Yat-sen University were enrolled.Participants in the study will be assigned to one of three treatment arms: Arm A: Participants will received conventional treatment and low dose of NK cells treatment for 4 times. Arm B: Participants will received conventional treatment and normal dose of NK cells treatment for 4 times. Arm C: Participants will received conventional treatment and normal dose of NK cells treatment for 8 times. The cultured NK cells from the peripheral blood of the same blood type were taken and infused at intervals of two weeks. Periodic liver function recheck and imaging examination were conducted for 6 months after the last NK cells infusion.

Official Title
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Safety Study of Nature Killer Cells From Sibship to Treat the Recurrence of Hepatocellular Carcinoma After Liver Transplantation

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: Low Dose NK cells ×4 times
* Biological: Normal Dose NK cells ×4 times
* Biological: Normal Dose NK cells ×8 times


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Proved hepatocellular carcinoma histologically after liver transplantation. Confirmed recurrence of hepatocellular carcinoma by CT/MRI. The same blood type relatives with blood transmitted diseases negative. Written informed consent. Exclusion Criteria: Autoimmune diseases require long-term of glucocorticoid. Other candidates who are judged to be not applicable to this study by investigators. Poor compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Received conventional treatment and NK cells once per two-week for the first two-month, at a dose of 5×10E9 NK cells. | Biological: Low Dose NK cells ×4 times<br>* Received conventional treatment and NK cells once per two-week for the first two-month, at a dose of 5×10E9 NK cells.<br>* Other names: low dose Natural killer cells ×4 times;|
| Experimental: Arm B<br>Received conventional treatment and NK cells once per two-week for the first two-month, at a dose of 1×10E10 NK cells. | Biological: Normal Dose NK cells ×4 times<br>* Received conventional treatment and NK cells once per two-week for the first two-month, at a dose of 1×10E10 NK cells.<br>* Other names: normal dose Natural killer cells ×4 times;|
| Experimental: Arm C<br>Received conventional treatment and NK cells once per two-week for the first four-month, at a dose of 1×10E10 NK cells. | Biological: Normal Dose NK cells ×8 times<br>* Received conventional treatment and NK cells once per two-week for the first four-month, at a dose of 1×10E10 NK cells.<br>* Other names: normal dose Natural killer cells ×8 times;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GVHD | Rash, fever, diarrhea, jaundice etc. leukocyte, platelet, red blood cells reduce, abnormal liver function.Pathological biopsy if necessary. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute rejection | abnormal liver function，pathological biopsy if necessary. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK cells, Liver Transplantation, Hepatocellular Carcinoma Recurrence