Safety Study of Liver Natural Killer Cell Therapy for Hepatoma Liver Transplantation

Hepatocellular Carcinoma Clinical Trial

— MIAMINK  

Official title:

A Novel Immunotherapy for Liver Transplant Patients With Hepatocellular Carcinoma: Anti-tumor Effect of IL2-activated Donor Liver Natural Killer Cell

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01147380
• Other study ID #: 20100344
• Secondary ID: 20100344
• Status: Completed
• Phase: Phase 1
• First received: June 17, 2010
• Last updated: February 11, 2016
• Start date: June 2010
• Est. completion date: December 2014

Study information

• Verified date: February 2016
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Evidence of Liver Transplantation
• Hepatocellular Carcinoma
• Liver Cirrhosis

Intervention

Biological:
• Liver NK cell inoculation
Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation.

Locations

Country	Name	City	State
United States	University of Miami	Miami	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Seigo Nishida	Florida Department of Health

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	1 year	No
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.	1 year	Yes
Secondary	Anti-HCC Effect of This Treatment		2 year	No
Secondary	Anti-HCV Effect of This Treatment (If Applicable)		2 year	No