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A Study of TCR-Redirected T Cell Infusion in Subject With Recurrent HBV-related HCC Post Liver Transplantation

Primary Purpose

Recurrent Hepatocellular Carcinoma

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Biological: TCR-T
Sponsored by
Lion TCR Pte. Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Hepatocellular Carcinoma

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis as hepatocellular carcinoma (HCC)
  • Underwent liver transplantation and confirmed recurrent HCC post operation
  • Seropositive for hepatitis B surface antigen
  • No major post-operative complication
  • Life expectancy of at least 12 weeks
  • Ability to provide informed consent
  • Ability to comply with study procedures
  • HLA profile matching with HLA-class I restriction element of the available T cell receptors

Exclusion Criteria:

  • Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR-T, stem cells or combined therapy of the kind within 3 months prior to enrolment
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
  • Likelihood to require steroid treatment during the period of the clinical trial
  • Any other concurrent liver infections such as hepatitis A, C or D infection
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
  • Known Central Nervous System tumours including metastatic brain disease.
  • Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study
  • Patients with reproductive potential who tested positive for serum or urine pregnancy test result within 14 days prior to enrolment.

Sites / Locations

  • Third Affiliated Hospital of Sun Yat-sen UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HBV/TCR T cell Infusion

Arm Description

This is a single-arm study. Patients will receive a total of 2 cycles, in which first 28-day treatment cycle consists of escalating doses of TCR-T on Day 1, Day 8, Day 15 and Day 22, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of second (final) cycle. A one month treatment break will be given between the cycles.

Outcomes

Primary Outcome Measures

Safety of the TCR-T treatment

Secondary Outcome Measures

Efficacy of induction of tumor specific T cell responses as measured by the persistence of HBV specific T cells in peripheral blood samples at several time points following adoptive transfer
Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline

Full Information

First Posted
March 21, 2016
Last Updated
November 15, 2018
Sponsor
Lion TCR Pte. Ltd.
Collaborators
Agency for Science, Technology and Research, Third Affiliated Hospital, Sun Yat-Sen University
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1. Study Identification

Unique Protocol Identification Number
NCT02719782
Brief Title
A Study of TCR-Redirected T Cell Infusion in Subject With Recurrent HBV-related HCC Post Liver Transplantation
Official Title
A Phase I Study T Cell Receptor-Redirected T Cells Infusions in Subjects With Recurrent HBV-Related Hepatocellular Carcinoma in Post Liver Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
November 2018
Overall Recruitment Status
Unknown status
Study Start Date
July 2, 2015 (Actual)
Primary Completion Date
May 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lion TCR Pte. Ltd.
Collaborators
Agency for Science, Technology and Research, Third Affiliated Hospital, 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 10 patients with Hepatitis B virus (HBV) related HCC who underwent liver transplantation and are confirmed to have recurrent HCC. 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
This is a phase I, single armed and open labelled trial in patients with recurrent HBV related HCC after liver transplantation. Subjects who meet eligibility criteria will receive escalating doses of HBV specific T cell receptor (TCR-T) on Day 1, Day 8, Day 15 and Day 22 of the first 28-day treatment cycle, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of repeated cycle. A 21-day treatment break will be given between each cycle. Treatment will be continued until disease progression unless otherwise specified per investigator's discretion. Subjects will be followed up post treatment for safety monitoring, including monthly follow up for the first three month and every 2-monthly follow up up to 24 months post treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HBV/TCR T cell Infusion
Arm Type
Experimental
Arm Description
This is a single-arm study. Patients will receive a total of 2 cycles, in which first 28-day treatment cycle consists of escalating doses of TCR-T on Day 1, Day 8, Day 15 and Day 22, followed by every 2-week dosing on Day 1, Day 15, Day 29 and Day 43 of second (final) cycle. A one month treatment break will be given between the cycles.
Intervention Type
Biological
Intervention Name(s)
Biological: TCR-T
Intervention Description
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
Primary Outcome Measure Information:
Title
Safety of the TCR-T treatment
Time Frame
Start of treament until 1 month after last treatment
Secondary Outcome Measure Information:
Title
Efficacy of induction of tumor specific T cell responses as measured by the persistence of HBV specific T cells in peripheral blood samples at several time points following adoptive transfer
Time Frame
Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment
Title
Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline
Time Frame
Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment
Other Pre-specified Outcome Measures:
Title
1-year PFS (progression free survival) which is measured by the number of patients with stable disease after 1 year, using mRECIST
Time Frame
Start of treatment until disease progression, median 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis as hepatocellular carcinoma (HCC) Underwent liver transplantation and confirmed recurrent HCC post operation Seropositive for hepatitis B surface antigen No major post-operative complication Life expectancy of at least 12 weeks Ability to provide informed consent Ability to comply with study procedures HLA profile matching with HLA-class I restriction element of the available T cell receptors Exclusion Criteria: Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR-T, stem cells or combined therapy of the kind within 3 months prior to enrolment Second primary malignancy that is clinically detectable at the time of consideration for study enrolment Likelihood to require steroid treatment during the period of the clinical trial Any other concurrent liver infections such as hepatitis A, C or D infection Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection Known Central Nervous System tumours including metastatic brain disease. Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study Patients with reproductive potential who tested positive for serum or urine pregnancy test result within 14 days prior to enrolment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Grace Khoo Koay
Phone
(65) 69260818
Email
clinicaltrials@liontcr.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaofang Zheng
Phone
86-(020)-8217-9791
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qi Zhang, MD
Organizational Affiliation
Third Affiliated Hospital, Sun Yat-Sen University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Antonio Bertoletti, MD
Organizational Affiliation
Duke-NUS Graduate Medical School
Official's Role
Study Chair
Facility Information:
Facility Name
Third Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510630
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qi Zhang, Ph.D, MD
Phone
(86)20-85253106

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 in Subject With Recurrent HBV-related HCC Post Liver Transplantation

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