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

Recurrent Hepatocellular Carcinoma Clinical Trial

Official title:

Phase I Study of T Cell Receptor-Redirected T Cells With Recurrent HBV Treatment in Patients-Related Hepatocellular Carcinoma in Post Liver Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04677088
• Other study ID #: LTCR-HCC-2-2
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 29, 2018
• Est. completion date: December 2021

Study information

• Verified date: December 2020
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 7
• Est. completion date: December 2021
• Est. primary completion date: February 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Recurrent Hepatocellular Carcinoma

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun-Yat Sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Xiaoshun He	Lion TCR Pte. Ltd.

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View Citation

Koh S, Shimasaki N, Suwanarusk R, Ho ZZ, Chia A, Banu N, Howland SW, Ong AS, Gehring AJ, Stauss H, Renia L, Sällberg 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:e114. doi: 10.1038/mtna.2013.43. — View 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety evaluation of the TCR-T treatment	Incidence of adverse events/serious adverse events	Start of Treatment until 28 days post last dose
Secondary	Overall Response Rate	Tumour assessment will be according to RECIST v1.1. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to RECIST v1.1 from baseline.	Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment.
Secondary	Progression-free survival (PFS)	1-year PFS is measured by the number of patients with stable disease after 1 year, using RECIST v1.1.	Start of treatment until disease progression, and at 6-month and 1-year.
Secondary	Overall survival (OS)	OS is defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for two years.	Start of treatment until disease progression, and at 6-month and 1-year.