Nasopharyngeal CarcinomaPhase 2NCT03648697
EBV-TCR-T（YT-E001）for Patients With EBV-positive Recurrent or Metastatic NPC
A Phase 2 study testing EBV-TCR-T (YT-E001) cells in people with Nasopharyngeal Carcinoma, run by Fujian Cancer Hospital at 1 site in China.
Trial summary
TCR-T cell therapy experienced a breakthrough for treating tumors in recent years. Phase I / II trial of NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma conducted by the Rosenberg team at the National Cancer Institute showed that 61% Synovial cell sarcoma and 55% melanoma had therapeutic responses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nasopharyngeal Carcinoma
- What is being tested?
- EBV-TCR-T (YT-E001) cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 10 Oct 2018to 10 Oct 2021
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years old;
- Sign an informed consent before undertaking any trial-related activities;
- NPC patients diagnosed by licensed pathologist, EBV DNA copy number >500.
- Received at least one run of standard therapy (surgery, chemo, radiation and targeted therapy) or first line and second line treatment failure;
- HLA-A*0201/2402/1101;
- ECOG score 0-2；Life expectancy is longer than 3 months;
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- No Chinese herbal medicine usage within 4 weeks before enrollment;
- Lab test results meet the following requirements:
- White blood cell count≥4.0×109/L; ANC≥1.5 ×109/L; PLT≥100 ×109/L; Hemoglobin≥90g/L; Prothrombin time or INR ≤1.5× normal upper limit, except taking anticoagulant therapy; PTT≤1.5× normal upper limit；AST≤3×ULN; ALT≤3×ULN; ALP≤3×ULN; TBIL≤1.5×ULN。
- Levels of calcium, potassium, and magnesium in serum are within the normal range;
- Pregnancy test is negative for female subjects with reproductive capability before participating the study Female subjects must consent using birth control during the study or prohibit any homo or heterosexual behavior;
- Can regularly visit the research institutions for tests, evaluations, and monitoring throughout the study period.
Who cannot join
- Received major surgery, conventional chemotherapy, large-area radiotherapy, immune therapy or any biological anti-tumor therapy within 4 weeks prior to the study;
- Allergic to any components of the therapy;
- Never recovered to <2 grade CTCAE from prior surgery or treatment-related adverse events;
- With two or other types of primary solid tumors;
- Poorly managed hypertension (systolic blood pressure >160 mmHg and / or diastolic blood pressure > 90 mmHg) or clinically significant(for example, active) cardiovascular and cerebrovascular diseases such as cerebrovascular incident (within 6 months prior to signing the informed consent), myocardial infarction (within 6 months prior to signing the informed consent), unstable angina, grade II or above heart failure, Congestive, or severe arrhythmia can not be controlled by medication or has a potential impact on the study;
- With other serious organic disease and/or mental illness;
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- With systemic active infections that need treatments, including active tuberculosis, HIV/HBV/HCV- positive or clinically active hepatitis A, B and C;
- With autoimmune diseases: such as a history of inflammatory bowel disease (IBD) or other autoimmune diseases determined by the investigator to be unsuitable for the study (e.g. systemic lupus erythematosus (SLE), vasculitis, invasive pulmonary disease);
- Within 4 weeks prior the infusion, received chronic systemic steroid cortisone, Hydroxyurea, immunomodulatory treatment (for example: Interleukin 2, alpha or gamma interferon, GCSF, cyclosporine etc.);
- History of organ allografts, autologous / allogeneic stem cell transplantation, and renal replacement therapy;
- With central nervous system metastasis.
- With uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease, or liver failure;
- Pregnant or lactating female patients;
- Received concomitant medication prohibited by the protocol;
- With any medical condition or disease determined by the investigators that may be detrimental to this trial;
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
Jianji Pan, 0591-83660063, panjianji@126.com
About this study
Official title: A Pilot Study of EBV-TCR-T(YT-E001) in NPC Patients
TCR-T cell therapy experienced a breakthrough for treating tumors in recent years. Phase I / II trial of NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma conducted by the Rosenberg team at the National Cancer Institute showed that 61% Synovial cell sarcoma and 55% melanoma had therapeutic responses. These and lots of clinical achievements indicate that TCR-T cell therapy can target a variety of tumors including solid tumors without any severe side effects found in CAR-T trials.
Nasopharyngeal carcinoma (NPC), a kinds of head-neck malignant tumor, which used to appear mostly in southern China (especially in Fujian and Guangdong and Guangxi provinces). Most patients with NPC show evidence of infection with the Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage NPC, and play a role in causing and inducing the disease program and development. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if EBV antigen special T cells (YT-E001) could recognize and kill special parts of EBV infected cells, and finally inhibit the tumor recurrence or metastasis of NPC patients.
Read more
This study will focus on the NPC highly expressed EBV antigen such as LMP1, LMP2 and EBNA1，the high affinity TCR target the above EBV antigen were screened from the healthy donor using the sorting and single cell cloning technique. Then, using the lentivirus to transduce the TCR gene to the autologous T cells.
This study will investigate the safety and tolerability of EBV-TCR-T cell therapy in subjects with NPC who had received prior therapy for their disease but their disease has progressed or relapsed.
The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and fludarabine. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly used for lymphodepletion in immunotherapy clinical trials.
Read the detailed description
This Phase I/II study is designed as single dose pilot trial evaluating the safety and of EBV-TCR-TT cell therapy in subjects with NPC who have received prior therapy for their disease but the disease has progressed or relapsed. Anti-tumor activity and other exploratory objectives will be assessed. Subjects enter from a Screening Protocol and are positive for HLA- A02:01/24:02/11:01, and EBV serum positive. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -6 and -4 followed by infusion of dose of about 2×108 EBV-TCR-T(YT-E001).
Subjects will stay in hospital for safety and efficacy assessment daily from T cell infusion (Day 0) through Day 7, and then weekly until week 4 and then at 8 weeks every 8 weeks until progression of their disease or the end or termination of trial.
- Conditions
- Nasopharyngeal Carcinoma
- Being tested
- EBV-TCR-T (YT-E001) cells
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EBV-TCR-T (YT-E001) cellsBiological
Also called Fludarabine, Cyclophosphamide
EBV-TCR-T (YT-E001) cells are prepared via lentiviral infection. 6-10 days prior to infusion of TCR-T cells (YT-E001), subjects receive fludarabine at dose 30mg/m2/day for 4 days and cyclophosphamide treatment at dose 30mg/kg/day for 2 days and take a rest for one day before infusion.
Patients, who receive an infusion of YT-E001, will remain in the hospital to be monitored for adverse events until they have recovered from the treatment. Patients will have frequent follow-up visit to monitor the persistence of modified T cells and efficacy of the treatment.
| Study group | Role | What they receive |
|---|---|---|
| EBV-TCR-T cells(YT-E001) | Experimental | EBV-TCR-T (YT-E001) cells are prepared via lentiviral infection. 6-10 days prior to infusion of TCR-T cells (YT-E001), subjects receive fludarabine at dose 30mg/m2/day for 4 days and cyclophosphamide treatment at dose 30mg/kg/day for 2 days and take a rest for one day before infusion.
A single dose of EBV-TCR(YT-E001) transduced T cells (about 2×108) will be intravenously (i.v.) administered. Receives: Biological: EBV-TCR-T (YT-E001) cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events
To evaluate the safety and feasibility of the administration of EBV-TCR transduced T cells(YT-E001) in patients with EBV+ NPC.
Measured: 60 days
Secondary outcomes (1)
Number of participants with clinical responses
To evaluate the efficacy of EBV positive NPC patients treated with EBV antigen specific affinity-enhanced TCR transduced autologous T cell therapy(YT-E001).
Measured: 1 YEAR
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2018
- Study start10 Oct 2018
- Primary completion8 Oct 2021 (estimated)
- Study completion10 Oct 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Fujian Cancer HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open label, single dose phase I/II study of safety and efficacy.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Cancer Hospital
- Sponsor type
- Other government
- Collaborators
- China Immunotech (Beijing) Biotechnology Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03648697
- Sponsor's protocol ID
- HXYT-001
- Status last verified
- Aug 2020
- First submitted
- 24 Aug 2018
- Last updated
- 11 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of EBV-TCR-T(YT-E001) in NPC Patients
- ClinicalTrials.gov ID
- NCT03648697
- Acronym / sponsor ID
- HXYT-001
- Conditions
- Nasopharyngeal Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Fujian Cancer HospitalOther government
- Collaborators
- China Immunotech (Beijing) Biotechnology Co., Ltd.
- Study start
- 10 Oct 2018 (actual)
- Primary completion
- 8 Oct 2021 (estimated)
- Study completion
- 10 Oct 2021 (estimated)
- First posted
- 27 Aug 2018 (actual)
- 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.
TCR-T cell therapy experienced a breakthrough for treating tumors in recent years. Phase I / II trial of NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma conducted by the Rosenberg team at the National Cancer Institute showed that 61% Synovial cell sarcoma and 55% melanoma had therapeutic responses. These and lots of clinical achievements indicate that TCR-T cell therapy can target a variety of tumors including solid tumors without any severe side effects found in CAR-T trials.
Nasopharyngeal carcinoma (NPC), a kinds of head-neck malignant tumor, which used to appear mostly in southern China (especially in Fujian and Guangdong and Guangxi provinces). Most patients with NPC show evidence of infection with the Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage NPC, and play a role in causing and inducing the disease program and development. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if EBV antigen special T cells (YT-E001) could recognize and kill special parts of EBV infected cells, and finally inhibit the tumor recurrence or metastasis of NPC patients.
This study will focus on the NPC highly expressed EBV antigen such as LMP1, LMP2 and EBNA1，the high affinity TCR target the above EBV antigen were screened from the healthy donor using the sorting and single cell cloning technique. Then, using the lentivirus to transduce the TCR gene to the autologous T cells.
This study will investigate the safety and tolerability of EBV-TCR-T cell therapy in subjects with NPC who had received prior therapy for their disease but their disease has progressed or relapsed.
The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and fludarabine. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly used for lymphodepletion in immunotherapy clinical trials.
Detailed description
This Phase I/II study is designed as single dose pilot trial evaluating the safety and of EBV-TCR-TT cell therapy in subjects with NPC who have received prior therapy for their disease but the disease has progressed or relapsed. Anti-tumor activity and other exploratory objectives will be assessed. Subjects enter from a Screening Protocol and are positive for HLA- A02:01/24:02/11:01, and EBV serum positive. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -6 and -4 followed by infusion of dose of about 2×108 EBV-TCR-T(YT-E001).
Subjects will stay in hospital for safety and efficacy assessment daily from T cell infusion (Day 0) through Day 7, and then weekly until week 4 and then at 8 weeks every 8 weeks until progression of their disease or the end or termination of trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open label, single dose phase I/II study of safety and efficacy.
| Arm | Type | Receives |
|---|---|---|
| EBV-TCR-T cells(YT-E001) | Experimental | Biological: EBV-TCR-T (YT-E001) cellsEBV-TCR-T (YT-E001) cells are prepared via lentiviral infection. 6-10 days prior to infusion of TCR-T cells (YT-E001), subjects receive fludarabine at dose 30mg/m2/day for 4 days and cyclophosphamide treatment at dose 30mg/kg/day for 2 days and take a rest for one day before infusion. A single dose of EBV-TCR(YT-E001) transduced T cells (about 2×108) will be intravenously (i.v.) administered. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- ≥18 years old;
- Sign an informed consent before undertaking any trial-related activities;
- NPC patients diagnosed by licensed pathologist, EBV DNA copy number >500.
- Received at least one run of standard therapy (surgery, chemo, radiation and targeted therapy) or first line and second line treatment failure;
- HLA-A*0201/2402/1101;
Key exclusion criteria (15 listed)
- Received major surgery, conventional chemotherapy, large-area radiotherapy, immune therapy or any biological anti-tumor therapy within 4 weeks prior to the study;
- Allergic to any components of the therapy;
- Never recovered to <2 grade CTCAE from prior surgery or treatment-related adverse events;
- With two or other types of primary solid tumors;
- Poorly managed hypertension (systolic blood pressure >160 mmHg and / or diastolic blood pressure > 90 mmHg) or clinically significant(for example, active) cardiovascular and cerebrovascular diseases such as cerebrovascular incident (within 6 months prior to signing the informed consent), myocardial infarction (within 6 months prior to signing the informed consent), unstable angina, grade II or above heart failure, Congestive, or severe arrhythmia can not be controlled by medication or has a potential impact on the study;
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 |
|---|---|---|
| EBV-TCR-T (YT-E001) cellsAlso: Fludarabine, CyclophosphamideEBV-TCR-T (YT-E001) cells are prepared via lentiviral infection. 6-10 days prior to infusion of TCR-T cells (YT-E001), subjects receive fludarabine at dose 30mg/m2/day for 4 days and cyclophosphamide treatment at dose 30mg/kg/day for 2 days and take a rest for one day before infusion. Patients, who receive an infusion of YT-E001, will remain in the hospital to be monitored for adverse events until they have recovered from the treatment. Patients will have frequent follow-up visit to monitor the persistence of modified T cells and efficacy of the treatment. | Biological | EBV-TCR-T cells(YT-E001) |
Primary outcome
Number of participants with adverse events
Time frame: 60 days
To evaluate the safety and feasibility of the administration of EBV-TCR transduced T cells(YT-E001) in patients with EBV+ NPC.
1 secondary outcome
Number of participants with clinical responses
Time frame: 1 YEAR
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2020.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EBV-TCR-T (YT-E001) cells in people with Nasopharyngeal Carcinoma, run by Fujian Cancer Hospital 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 12 inclusion and 15 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 11 Aug 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 JianJi Pan (0591-83660063, panjianji@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (time frame: 60 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Aug 2020.