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

NCT01147380 | Completed Phase 1 Results DMC

• 1 other identifier: 20100344
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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)

Conditions

Liver Cirrhosis; Hepatocellular Carcinoma; Evidence of Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• NK Cell Infusion-related Toxicity

  1 year

• Anti-HCC Effect of This Treatment

  2 year

• Anti-HCV Effect of This Treatment (If Applicable)

  2 year

Study Arms (2)

Small dose

EXPERIMENTAL

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

Large dose

EXPERIMENTAL

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

Interventions

Liver NK cell inoculation BIOLOGICAL

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

Large dose; Small dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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),

Sponsors & Collaborators

• Seigo Nishida: lead
• Florida Department of Health: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33176, United States

Location

Related Publications (1)

• 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.

  PMID: 34282496 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Dr. Seigo Nishida
• Organization: University of Miami

snishida@med.miami.edu

305-355-5760

Study Officials

• Seigo Nishida, MD PhD

  Department of Surgery, University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of clinical surgery

Study Record Dates

• First Submitted: June 17, 2010
• First Posted: June 22, 2010
• Study Start: June 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 10, 2016
• Results First Posted: March 10, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)