TCR-Redirected T Cell Treatment in Patients With Recurrent HBV-related Hepatocellular Carcinoma Post Liver Transplantation

NCT ID: NCT04677088

Last Updated: 2020-12-21

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

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-29

Study Completion Date

2021-12-31

Brief Summary

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This is a single-arm and open-label study to assess the safety, tolerability and primary efficacy of the HBV specific T cell receptor (HBV/TCR) redirected T cell in patients with recurrent Hepatitis B virus (HBV) related hepatocellular carcinoma post liver transplantation.

Detailed Description

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Conditions

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Recurrent Hepatocellular Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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HBV/ TCR T cell infusion

Autologous T cells with HBV antigen-specific TCR

Group Type EXPERIMENTAL

TCR-T cells

Intervention Type BIOLOGICAL

Patients will receive 1 x 10\^4 cells/kg to 5 x 10\^6 cells/kg bodyweight of TCR redirected T cells by IV infusion.

Interventions

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TCR-T cells

Patients will receive 1 x 10\^4 cells/kg to 5 x 10\^6 cells/kg bodyweight of TCR redirected T cells by IV infusion.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Diagnosis as hepatocellular carcinoma (HCC).
2. Recurrent locally advanced and/or metastatic hepatocellular carcinoma (HCC) post liver transplantation.
3. Seropositive for hepatitis B surface antigen, or presence of HBV DNA or HBV RNA.
4. HLA profile matching with HLA-class I restriction element of the available T cell receptors.
5. ECOG performance status ≤ 2.
6. Laboratory criteria:

1. Liver function: ALT and AST ≤ 5 of upper limit of normal (ULN), TBIL ≤ 3 x ULN.
2. Neutrophil cell number ≥1.5×10\^9/L.
3. Platelet count ≥100×10\^9/L.
7. Ability to provide informed consent.
8. Willing and able to comply with all study procedures.

Exclusion Criteria

1. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment.
2. Likelihood to require steroid treatment during the period of the clinical trial.
3. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples.
4. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
5. Administration of any other cell therapy, including NK, CIK, DC, CTL, CAR- T, stem cells or combined therapy of the kind within 28 days prior to start of treatment.
6. 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

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lion TCR Pte. Ltd.

INDUSTRY

Sponsor Role collaborator

Xiaoshun He

OTHER

Sponsor Role lead

Responsible Party

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Xiaoshun He

MD.

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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The First Affiliated Hospital of Sun-Yat Sen University

Guangzhou, Guangdong, China

Site Status

Countries

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China

References

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Tan AT, Yang N, Lee Krishnamoorthy T, Oei V, Chua A, Zhao X, Tan HS, Chia A, Le Bert N, Low D, Tan HK, Kumar R, Irani FG, Ho ZZ, Zhang Q, Guccione E, Wai LE, Koh S, Hwang W, Chow WC, Bertoletti A. Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy. Gastroenterology. 2019 May;156(6):1862-1876.e9. doi: 10.1053/j.gastro.2019.01.251. Epub 2019 Jan 31.

Reference Type BACKGROUND
PMID: 30711630 (View on PubMed)

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-2-2

Identifier Type: -

Identifier Source: org_study_id