Clinical trial NCT02686372: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: hepatocellular carcinoma
hepatitis B virus-related
post liver transplantation
HCC
Lead sponsor: Lion TCR Pte. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: First Affiliated Hospital, Sun Yat-Sen University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
First posted: 2016-02-19
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: To Evaluate safety of the TCR-T treatment
timeFrame: Start of Treatment until 28 days post last dose
Secondary outcomes:
measure: To evaluate Progression Free Survival rate
timeFrame: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
measure: To evaluate Duration of response rate
timeFrame: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
measure: To evaluate objective response rate
timeFrame: Start of Treatment until disease progression, and subsequent follow up for 2 years or death (whichever comes first)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun-Yat Sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Xiaoshun He, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.