A Study of TCR-Redirected T Cell Infusion to Prevent Hepatocellular Carcinoma Recurrence Post Liver Transplantation

NCT ID: NCT02686372

Last Updated: 2022-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-16

Study Completion Date

2021-09-28

Brief Summary

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Hepatocellular Carcinoma (HCC) recurrence rate is high among liver transplant patients, while treatment measures are limited. This study plans to recruit 39 subjects with Hepatitis B virus (HBV) related HCC after liver transplantation. The objective of the study is to assess the safety, tolerability and effectiveness of the HBV specific T cell receptor (HBV/TCR) redirected T cell in the target population.

Detailed Description

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A open-label, cohort clinical study of T cell receptor-redirected T cells to prevent recurrence of HBV-related hepatocellular carcinoma after liver transplantation. Subjects will be enrolled into the observation cohort or treatment cohort.

Subjects enrolled in the treatment group will receive escalating doses of HBV/ TCR expressing autologous T cells after confirming eligibility. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse.

Upon disease recurrence, eligible patient may receive HBV specific T-cell receptor (TCR-T) treatment.

Conditions

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Hepatocellular Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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HBV/TCR-T cell infusion

Subjects enrolled in the experimental (treatment) group will receive escalating doses of HBV/ TCR expressing autologous T cells. The interval between the first two doses is 14 days, followed by one month of safety monitoring, before subsequent two doses of 1 month interval in between. Thereafter, subjects would enter into observation period of the safety and tolerability of the treatment and will be followed up until disease relapse.

Group Type EXPERIMENTAL

TCR-T

Intervention Type BIOLOGICAL

Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

No intervention and TCR-T (at crossover)

No intervention and to be crossover to experimental arm upon confirmation of disease recurrence.

Group Type OTHER

No intervention and TCR-T (at crossover)

Intervention Type BIOLOGICAL

Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

Interventions

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TCR-T

Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

Intervention Type BIOLOGICAL

No intervention and TCR-T (at crossover)

Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Diagnosis as hepatocellular carcinoma (HCC)
* Underwent liver transplantation
* Seropositive for hepatitis B surface antigen (HBsAg), or presence of HBV DNA or HBV RNA before liver transplantation
* Expression of TCR-T target epitopes within specific human leukocyte antigen (HLA) class I profile
* No major post-operative complication
* Life expectancy of at least 3 months
* Ability to provide informed consent
* Ability to comply with study procedures

Exclusion Criteria

* Known, clinically suspected or has history or central nervous system (CNS) and bone metastasis
* Significant ongoing immunologic rejection based on pathology and clinical diagnosis
* Evidence or history of significant bleeding diathesis or coagulopathy
* Prior exposure to any cell therapy such as, but not limited to NK, CIK, DC, CTL, stem cells therapy
* Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS)
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
* Women who are pregnant or breast-feeding
* Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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First Affiliated Hospital, Sun Yat-Sen University

OTHER

Sponsor Role collaborator

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role collaborator

Lion TCR Pte. Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Xiaoshun He, MD

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital, Sun Yat-Sen University

Locations

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The First Affiliated Hospital, Sun-Yat Sen University

Guangzhou, Guangdong, China

Site Status

Countries

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China

References

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Qasim W, Brunetto M, Gehring AJ, Xue SA, Schurich A, Khakpoor A, Zhan H, Ciccorossi P, Gilmour K, Cavallone D, Moriconi F, Farzhenah F, Mazzoni A, Chan L, Morris E, Thrasher A, Maini MK, Bonino F, Stauss H, Bertoletti A. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient. J Hepatol. 2015 Feb;62(2):486-91. doi: 10.1016/j.jhep.2014.10.001. Epub 2014 Oct 13.

Reference Type BACKGROUND
PMID: 25308176 (View on PubMed)

Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A. Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines. J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23.

Reference Type BACKGROUND
PMID: 21145860 (View on PubMed)

Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sallberg M, Campana D, Bertoletti A. A practical approach to immunotherapy of hepatocellular carcinoma using T cells redirected against hepatitis B virus. Mol Ther Nucleic Acids. 2013 Aug 13;2(8):e114. doi: 10.1038/mtna.2013.43.

Reference Type BACKGROUND
PMID: 23941866 (View on PubMed)

Other Identifiers

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LTCR-HCC-1-1

Identifier Type: -

Identifier Source: org_study_id

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