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

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TCR-T
No intervention and TCR-T (at crossover)
Sponsored by
Lion TCR Pte. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hepatocellular Carcinoma focused on measuring hepatocellular carcinoma, hepatitis B virus-related, post liver transplantation, HCC

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The First Affiliated Hospital, Sun-Yat Sen University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

HBV/TCR-T cell infusion

No intervention and TCR-T (at crossover)

Arm Description

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.

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

Outcomes

Primary Outcome Measures

To Evaluate safety of the TCR-T treatment
Measures include - assessments of Adverse Events (AEs) and Serious AEs,

Secondary Outcome Measures

To evaluate Progression Free Survival rate
PFS
To evaluate Duration of response rate
DOR
To evaluate objective response rate
ORR

Full Information

First Posted
February 17, 2016
Last Updated
June 27, 2022
Sponsor
Lion TCR Pte. Ltd.
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
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1. Study Identification

Unique Protocol Identification Number
NCT02686372
Brief Title
A Study of TCR-Redirected T Cell Infusion to Prevent Hepatocellular Carcinoma Recurrence Post Liver Transplantation
Official Title
A Phase I Study of T Cell Receptor-Redirected T Cell Infusion For Prevention of Hepatocellular Carcinoma Recurrence in Subjects With Hepatitis B Virus-Related Hepatocellular Carcinoma Post Liver Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
May 16, 2018 (Actual)
Primary Completion Date
September 28, 2021 (Actual)
Study Completion Date
September 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lion TCR Pte. Ltd.
Collaborators
First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
hepatocellular carcinoma, hepatitis B virus-related, post liver transplantation, HCC

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HBV/TCR-T cell infusion
Arm Type
Experimental
Arm Description
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.
Arm Title
No intervention and TCR-T (at crossover)
Arm Type
Other
Arm Description
No intervention and to be crossover to experimental arm upon confirmation of disease recurrence.
Intervention Type
Biological
Intervention Name(s)
TCR-T
Intervention Description
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
Intervention Type
Biological
Intervention Name(s)
No intervention and TCR-T (at crossover)
Intervention Description
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
Primary Outcome Measure Information:
Title
To Evaluate safety of the TCR-T treatment
Description
Measures include - assessments of Adverse Events (AEs) and Serious AEs,
Time Frame
Start of Treatment until 28 days post last dose
Secondary Outcome Measure Information:
Title
To evaluate Progression Free Survival rate
Description
PFS
Time Frame
Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
Title
To evaluate Duration of response rate
Description
DOR
Time Frame
Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
Title
To evaluate objective response rate
Description
ORR
Time Frame
Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaoshun He, MD
Organizational Affiliation
First Affiliated Hospital, Sun Yat-Sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital, Sun-Yat Sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25308176
Citation
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.
Results Reference
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PubMed Identifier
21145860
Citation
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.
Results Reference
background
PubMed Identifier
23941866
Citation
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.
Results Reference
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A Study of TCR-Redirected T Cell Infusion to Prevent Hepatocellular Carcinoma Recurrence Post Liver Transplantation

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