Evidence of Liver Transplantation, Hepatocellular Carcinoma, Liver Cirrhosis
Conditions
Brief summary
The objective of this study is to evaluate feasibility and safety of the adoptive transfer of activated natural killer (NK) cells extracted from cadaveric donor liver graft perfusate for liver transplant recipients with hepatocellular carcinoma (HCC)
Detailed description
To investigate whether adoptive transfer of IL-2 stimulated NKcells extracted from cadaveric donor liver graft exudates into recipient with HCC will lead to prevent recurrence of HCC after liver transplantation. The method we plan to use is to collect NK cells from the cadaveric donor liver perfusate at the time of organ recovery. The perfusate will be condensed by centrifuging and liver mononuclear cells (LMNC) were isolated by gradient centrifugation. LMNC will be cultured with anti-CD3 antibody. LMNC will be separted into a CD3-/CD56+ NK cell fraction and a non-NK cell fraction. The purity of isolated fractions will be assessed by Flow cytometric analyses. NK cells will be cultured with human recombinant IL-2 in 10% RPMI at 37 ºC in a 5% CO2 incubator. NK cells will be infused intravenously to the recipient with HCC who have liver transplant from the same cadaveric donor at post operative day 4 in attempt to prevent the metastasis and recurrence of HCC.
Interventions
BIOLOGICALLiver NK cell inoculation
Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation.
Sponsors
Florida Department of Health
Seigo Nishida
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary liver transplant recipient with HCC * Patients need to meet the liver transplant eligibility criteria * Cardiac function; cardiac echo will indicate that ejection fraction (EF) \> 35% or right ventricular systolic pressure (RVSP) \< 50mmHg. Stress echo will show no ischemic lesion (if applicable). * Pulmonary function; SpO2 \>90% or PaO2 \> 60 mmHg, or CT will show no active pulmonary lesion. * Complete blood count; Platelet \> 20,000 /mm\^3, Hematocrit \> 20%, WBC \> 1,000 /mm\^3 * Eighteen years of age or older * Ability to provide informed consent * If female of childbearing potential: Must not be lactating, must have a negative serum B-human chorionic gonadotropin (HCG) test within 7 days prior to Day of Transplant, and must agree to practice an acceptable and reliable form of contraception during the study Ability to provide informed consent
Exclusion criteria
* Living donor liver transplant; a healthy person donates part of his or her liver to the recipient * Multiple organ transplants * Prior solid organ or bone marrow transplant recipients * Fluminant hepatic failure * The patients regularly receive the hemodialysis more than twice a week before liver transplant * Status 1 transplants; acute severe disease and defined as a patient with only recent development of liver disease who is in the intensive care unit of the hospital with a life expectancy without a liver transplant of fewer than 7 days * ABO incompatible transplants * Transplants utilizing livers from non-heart beating donors; the cardiac death donor * Recipients of investigational therapy within 90 days prior to transplant procedure * Acute viral illness * History of malignancy within 5 years, with exception of: Adequately treated localized squamous or basal cell carcinoma of the skin without evidence or recurrence, and/or Hepatocellular carcinoma * Illness other than primary liver disease (e.g., severe ischemic heart disease, left ventricular dysfunction, or pulmonary disease), which, in the opinion of the Investigator, may significantly increase the risk of the transplantation procedure * Current drug or alcohol abuse or, in the opinion of the Investigator, is at risk for poor compliance (no drug testing required) * Serology positive donor (HCV, HBsAg, HBcAb, HTLV-1, HTLV-3, EBVIgM) * Poor liver function donor (Total bilirubin \> 3.0 mg/dl, Prothrombin time \> 35 sec), * Patients who receive intercurrent chemotherapy at the time of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Side Effect of Cadaveric Donor Liver NK Cell Infusion | 1 year | Side effect of cadaveric donor liver NK cell infusion We will measure the occurence of the side effect of the liver NK cell infusion. We will monitor the patient condition clinically. If any side effect are noticed, we will record them and report to the data safety monitoring comittee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HCV Effect of This Treatment (If Applicable) | 2 year | — |
| NK Cell Infusion-related Toxicity | 1 year | To assess NK cell infusion -related toxicity at the bedside. We will monitor the patient and check the vital sign. If any side effect are noticed, we will record and report to the data safety monitoring comittee. |
| Anti-HCC Effect of This Treatment | 2 year | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Small Dose The number of inoculation cells is between 10 and 100 million cells.
Liver NK cell inoculation: Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation. | 6 |
| Large Dose The number of inoculation cells is between 100 and 1000 million cells
Liver NK cell inoculation: Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation. | 12 |
| Total | 18 |
Baseline characteristics
| Characteristic | Large Dose | Small Dose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 5 Participants | 15 Participants |
| Age, Continuous | 55.6 years | 59.5 years | 56.9 years |
| Region of Enrollment United States | 12 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 12 |
Outcome results
Primary
Side Effect of Cadaveric Donor Liver NK Cell Infusion
Side effect of cadaveric donor liver NK cell infusion We will measure the occurence of the side effect of the liver NK cell infusion. We will monitor the patient condition clinically. If any side effect are noticed, we will record them and report to the data safety monitoring comittee.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Dose | Side Effect of Cadaveric Donor Liver NK Cell Infusion | 0 participants |
| Large Dose | Side Effect of Cadaveric Donor Liver NK Cell Infusion | 0 participants |
Secondary
Anti-HCC Effect of This Treatment
Time frame: 2 year
Secondary
Anti-HCV Effect of This Treatment (If Applicable)
Time frame: 2 year
Secondary
NK Cell Infusion-related Toxicity
To assess NK cell infusion -related toxicity at the bedside. We will monitor the patient and check the vital sign. If any side effect are noticed, we will record and report to the data safety monitoring comittee.
Time frame: 1 year
Population: Participants were devided two group( small and large dose) as described based on the dose of infused cell numbers.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Small Dose | NK Cell Infusion-related Toxicity | 0 participants |
| Large Dose | NK Cell Infusion-related Toxicity | 0 participants |