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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

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

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

NCT ID

NCT01147380

First Posted

June 17, 2010

Last Updated

February 11, 2016

Sponsor

Seigo Nishida

Collaborators

Florida Department of Health

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

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

Time Frame

1 year

Secondary Outcome Measure Information:

Title

NK Cell Infusion-related Toxicity

Description

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

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

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

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

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