Safety Study of Liver Natural Killer Cell Therapy for Hepatoma Liver Transplantation (MIAMINK)

February 11, 2016 updated by: Seigo Nishida

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

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Miami, Florida, United States, 33176
        • University of Miami

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Small dose
From the donor liver perfusate, mononuclear cell will be extracted and cultured. Then, the cells will be stimulated with IL-2. The number of inoculation cells( mainly NK cells) is between 10 and 100 million cells. The cells will be given to the liver transplant recipient who had the same donor for liver and liver perfusate. Patient of this arm receive small dose of liver NK cell inoculation as described.
Biological: Liver NK cell inoculation
Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation.
Experimental: Large dose
From the donor liver perfusate, mononuclear cell will be extracted and cultured. Then, the cells will be stimulated with IL-2. The number of inoculation cells(mainly NK cells) is between 100 and 1000 million cells. The cells will be given to the liver transplant recipient who had the same donor for liver and liver perfusate.Patient of this arm receive large dose of liver NK cell inoculation as described.
Biological: Liver NK cell inoculation
Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Side Effect of Cadaveric Donor Liver NK Cell Infusion
Time Frame: 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.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NK Cell Infusion-related Toxicity
Time Frame: 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.
1 year
Anti-HCC Effect of This Treatment
Time Frame: 2 year
2 year
Anti-HCV Effect of This Treatment (If Applicable)
Time Frame: 2 year
2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seigo Nishida

Collaborators

Florida Department of Health

Investigators

  • Principal Investigator: Seigo Nishida, MD PhD, Department of Surgery, University of Miami

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

June 17, 2010

First Submitted That Met QC Criteria

June 17, 2010

First Posted (Estimate)

June 22, 2010

Study Record Updates

Last Update Posted (Estimate)

March 10, 2016

Last Update Submitted That Met QC Criteria

February 11, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20100344 (Other Identifier: University of Miami IRB number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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