Recurrent Hepatocellular CarcinomaPhase 1NCT02719782
A Study of TCR-Redirected T Cell Infusion in Subject With Recurrent HBV-related HCC Post Liver Transplantation
A Phase 1 study testing Biological: TCR-T in people with Recurrent Hepatocellular Carcinoma, run by Lion TCR Pte. Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Recurrent Hepatocellular Carcinoma
- What is being tested?
- Biological: TCR-T
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 2 Jul 2015to Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Xiaofang Zheng contact
China1 site, 1 recruiting
- Recruiting
Third Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510630
Qi Zhang, Ph.D, MD, (86)20-85253106
About this study
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
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.
Read the 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.
- Conditions
- Recurrent Hepatocellular Carcinoma
- Being tested
- Biological: TCR-T
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological: TCR-TBiological
Autologous T cells transfected with mRNA encoding HBV antigen-specific TCR
| Study group | Role | What they receive |
|---|---|---|
| HBV/TCR T cell Infusion | Experimental | 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. Receives: Biological: Biological: TCR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of the TCR-T treatment
Measured: Start of treament until 1 month after last treatment
Secondary outcomes (2)
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
Measured: Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment
Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline
Measured: Start of treatment until disease progression, and subsequent follow up up to 24 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2016 (estimated)
- Study start2 Jul 2015
- Primary completionMay 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Recurrent Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lion TCR Pte. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Agency for Science, Technology and Research, Third Affiliated Hospital, Sun Yat-Sen University
- Responsible party
- Sponsor
- Investigators
- Qi Zhang, MD, Principal investigator, Third Affiliated Hospital, Sun Yat-Sen UniversityAntonio Bertoletti, MD, Study chair, Duke-NUS Graduate Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02719782
- Sponsor's protocol ID
- LTCR-HCC-2-1
- Status last verified
- Nov 2018
- First submitted
- 21 Mar 2016
- Last updated
- 16 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25308176Gehring 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.
PubMed 21145860Koh 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.
PubMed 23941866Yang F, Zheng X, Koh S, Lu J, Cheng J, Li P, Du C, Chen Y, Chen X, Yang L, Chen W, Wong RW, Wai LE, Wang T, Zhang Q, Chen W. Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial. Hepatol Int. 2023 Aug;17(4):850-859. doi: 10.1007/s12072-023-10524-x. Epub 2023 Apr 17.
PubMed 37067675
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02719782
- Acronym / sponsor ID
- LTCR-HCC-2-1
- Conditions
- Recurrent Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Lion TCR Pte. Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Agency for Science, Technology and Research, Third Affiliated Hospital, Sun Yat-Sen University
- Study start
- 2 Jul 2015 (actual)
- Primary completion
- May 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 25 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBV/TCR T cell Infusion | Experimental | Biological: Biological: TCR-TThis 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. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biological: TCR-TAutologous T cells transfected with mRNA encoding HBV antigen-specific TCR | Biological | HBV/TCR T cell Infusion |
Primary outcome
Safety of the TCR-T treatment
Time frame: Start of treament until 1 month after last treatment
2 secondary outcomes
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2018.
- Background: PubMed 25308176Qasim 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.
- Background: PubMed 21145860Gehring 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.
- Background: PubMed 23941866Koh 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.
- Derived from this study: PubMed 37067675Yang F, Zheng X, Koh S, Lu J, Cheng J, Li P, Du C, Chen Y, Chen X, Yang L, Chen W, Wong RW, Wai LE, Wang T, Zhang Q, Chen W. Messenger RNA electroporated hepatitis B virus (HBV) antigen-specific T cell receptor (TCR) redirected T cell therapy is well-tolerated in patients with recurrent HBV-related hepatocellular carcinoma post-liver transplantation: results from a phase I trial. Hepatol Int. 2023 Aug;17(4):850-859. doi: 10.1007/s12072-023-10524-x. Epub 2023 Apr 17.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaofang Zheng contact
Qi Zhang, MD principal investigator
Third Affiliated Hospital, Sun Yat-Sen University
Antonio Bertoletti, MD study chair
Duke-NUS Graduate Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biological: TCR-T in people with Recurrent Hepatocellular Carcinoma, run by Lion TCR Pte. Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Grace Khoo Koay ((65) 69260818, clinicaltrials@liontcr.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of the TCR-T treatment (time frame: Start of treament until 1 month after last treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02719782, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2018.