NCT02686372

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_1 hepatocellular-carcinoma

Timeline
Completed

Started May 2018

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 17, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 19, 2016

Completed
2.2 years until next milestone

Study Start

First participant enrolled

May 16, 2018

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 28, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 28, 2021

Completed
Last Updated

June 30, 2022

Status Verified

June 1, 2022

Enrollment Period

3.4 years

First QC Date

February 17, 2016

Last Update Submit

June 27, 2022

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinomahepatitis B virus-relatedpost liver transplantationHCC

Outcome Measures

Primary Outcomes (1)

  • To Evaluate safety of the TCR-T treatment

    Measures include \- assessments of Adverse Events (AEs) and Serious AEs,

    Start of Treatment until 28 days post last dose

Secondary Outcomes (3)

  • To evaluate Progression Free Survival rate

    Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)

  • To evaluate Duration of response rate

    Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)

  • To evaluate objective response rate

    Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)

Study Arms (2)

HBV/TCR-T cell infusion

EXPERIMENTAL

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.

Biological: TCR-T

No intervention and TCR-T (at crossover)

OTHER

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

Biological: No intervention and TCR-T (at crossover)

Interventions

TCR-TBIOLOGICAL

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

HBV/TCR-T cell infusion
No intervention and TCR-T (at crossover)BIOLOGICAL

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

No intervention and TCR-T (at crossover)

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The First Affiliated Hospital, Sun-Yat Sen University

Guangzhou, Guangdong, 510080, China

Location

Related Publications (3)

  • 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.

    PMID: 25308176BACKGROUND

  • 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.

    PMID: 21145860BACKGROUND

  • 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.

    PMID: 23941866BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Study Officials

  • Xiaoshun He, MD

    First Affiliated Hospital, Sun Yat-Sen University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 17, 2016

First Posted

February 19, 2016

Study Start

May 16, 2018

Primary Completion

September 28, 2021

Study Completion

September 28, 2021

Last Updated

June 30, 2022

Record last verified: 2022-06

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)