Liver CirrhosisPhase 1MIAMINKNCT01147380
Safety Study of Liver Natural Killer Cell Therapy for Hepatoma Liver Transplantation
A Phase 1 study testing Liver NK cell inoculation in people with Liver Cirrhosis and Hepatocellular Carcinoma, run by Seigo Nishida at 1 site in United States.
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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Cirrhosis, Hepatocellular Carcinoma, Evidence of Liver Transplantation
- What is being tested?
- Liver NK cell inoculation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2010to Dec 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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)
Read the 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.
- Being tested
- Liver NK cell inoculation
- Medical subject headings
- Liver Cirrhosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liver NK cell inoculationBiological
Liver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Liver NK cell inoculation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (3)
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.
Measured: 1 year
Anti-HCC Effect of This Treatment
Measured: 2 year
Anti-HCV Effect of This Treatment (If Applicable)
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2010 (estimated)
- Study startJun 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seigo Nishida
- Sponsor type
- University, hospital or other
- Collaborators
- Florida Department of Health
- Responsible party
- Sponsor-investigator, Seigo Nishida, University of Miami
- Investigators
- Seigo Nishida, MD PhD, Principal investigator, Department of Surgery, University of Miami
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01147380
- Sponsor's protocol ID
- 20100344
- Other IDs
- 20100344
- Acronym
- MIAMINK
- Status last verified
- Feb 2016
- First submitted
- 17 Jun 2010
- Last updated
- 10 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 34282496
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel Immunotherapy for Liver Transplant Patients With Hepatocellular Carcinoma: Anti-tumor Effect of IL2-activated Donor Liver Natural Killer Cell
- ClinicalTrials.gov ID
- NCT01147380
- Acronym / sponsor ID
- MIAMINK / 20100344
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Seigo NishidaUniversity, hospital or other
- Collaborators
- Florida Department of Health
- Study start
- Jun 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 22 Jun 2010 (estimated)
- Results
- Posted 10 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Small dose | Experimental | Biological: Liver NK cell inoculationFrom 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. |
| Large dose | Experimental | Biological: Liver NK cell inoculationFrom 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liver NK cell inoculationLiver transplant recipients will receive once liver NK cell inoculation several days after liver transplantation. | Biological | Large dose, Small dose |
Primary outcome
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.
3 secondary outcomes
NK Cell Infusion-related Toxicity
Time frame: 1 year
Anti-HCC Effect of This Treatment
Time frame: 2 year
Anti-HCV Effect of This Treatment (If Applicable)
Time frame: 2 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34282496Ohira 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Seigo Nishida, MD PhD principal investigator
Department of Surgery, University of Miami
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Liver NK cell inoculation in people with Liver Cirrhosis and Hepatocellular Carcinoma, run by Seigo Nishida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Side Effect of Cadaveric Donor Liver NK Cell Infusion (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01147380, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2016.