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

Primary Purpose

Liver Cirrhosis, Hepatocellular Carcinoma, Evidence of Liver Transplantation

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Liver NK cell inoculation
Sponsored by
Seigo Nishida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Miami

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Small dose

Large dose

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Anti-HCC Effect of This Treatment
Anti-HCV Effect of This Treatment (If Applicable)

Full Information

First Posted
June 17, 2010
Last Updated
February 11, 2016
Sponsor
Seigo Nishida
Collaborators
Florida Department of Health
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1. Study Identification

Unique Protocol Identification Number
NCT01147380
Brief Title
Safety Study of Liver Natural Killer Cell Therapy for Hepatoma Liver Transplantation
Acronym
MIAMINK
Official Title
A Novel Immunotherapy for Liver Transplant Patients With Hepatocellular Carcinoma: Anti-tumor Effect of IL2-activated Donor Liver Natural Killer Cell
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Seigo Nishida
Collaborators
Florida Department of Health

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis, Hepatocellular Carcinoma, Evidence of Liver Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Small dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Large dose
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Liver NK cell inoculation
Intervention Description
Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation.
Primary Outcome Measure Information:
Title
Side Effect of Cadaveric Donor Liver NK Cell Infusion
Description
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
Secondary Outcome Measure Information:
Title
NK Cell Infusion-related Toxicity
Description
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
Title
Anti-HCC Effect of This Treatment
Time Frame
2 year
Title
Anti-HCV Effect of This Treatment (If Applicable)
Time Frame
2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seigo Nishida, MD PhD
Organizational Affiliation
Department of Surgery, University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34282496
Citation
Ohira M, Hotta R, Tanaka Y, Matsuura T, Tekin A, Selvaggi G, Vianna R, Ricordi C, Ruiz P, Nishida S, Tzakis AG, Ohdan H. Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma. Cancer Immunol Immunother. 2022 Mar;71(3):589-599. doi: 10.1007/s00262-021-03005-3. Epub 2021 Jul 19.
Results Reference
derived

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

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