Clinical trial NCT03925896: Phase I Trial of LMP2 Antigen-specific TCR T-cell Therapy for Recurrent and Metastatic NPC Patients
Official title: LMP2 Antigen-specific High-affinity T Cell Receptor (TCR)-Transduced Autologous T-cell Therapy for Recurrent and Metastatic Nasopharyngeal Carcinoma, an Open-label, Single-center, Phase I Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Nasopharyngeal Carcinoma
Keywords: EBV TCR-T cells
recurrent
metastatic
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-04-24
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, a single-arm, open-labeled clinical trial will be performed to determine the safety and efficacy of EBV TCR-T cells in the treatment of recurrent/metastatic nasopharyngeal carcinoma with positive EBV infection in the Chinese population.

Detailed description: All enrolled subjects will be infused with EBV TCR-T cells. The project which enrolls 27 patients, according to the patient's HLA subtypes will be divided into HLA-A2, HLA-A11, HLA-A24 three groups, 9 patients in each group. Using a dose climbing method, each group will be divided into three dose subgroups. In the first dose subgroup, 5×106/kg TCR-T cells will be returned, and in the second dose subgroup, 1×107/kg TCR-T cells will be returned. The third dose subgroup 5 x 107/kg TCR-T cells will be returned.

Eligibility criteria: Inclusion Criteria:

1. Patients with nasopharyngeal carcinoma diagnosed by pathology and EBV infection (EBERs positive ) ; 2.18-70 years old; 3.MHC-I is HLA-A2, HLA-A11 or HLA-A24 subtype; 4. Progression after second-line platinum-containing chemotherapy regimen, recurrent/metastatic nasopharyngeal carcinoma patients who are inoperable and non-radiable; 5. Based on the Response Evaluation Criteria in Solid Tumors version (RECIST 1.1), there are ≥ 1 measurable target lesions; 6. Expected survival time is more than 12 weeks; 7. ECOG score 0-2 points; 8. Patients with good bone marrow, kidney, liver, and heart, and lung function 9. Can establish the venous access required for the collection, no contraindications for white blood cell collection; 10. Male and female patients of the appropriate age must adopt a reliable method of contraception; 11. Those who understand the trial and have signed an informed consent form.

Exclusion Criteria:

1. Patients with symptomatic brain metastasis;
2. Other malignant tumors other than nasopharyngeal carcinoma within 5 years prior to enrollment, in addition to appropriate treatment of cervical carcinoma in situ, cutaneous basal or squamous cell carcinoma, localized prostate cancer or ductal carcinoma in situ after radical surgery ;
3. Hepatitis B or hepatitis C active period, HIV-infected;
4. Any other uncontrolled active disease that impedes participation in the trial;
5. Patients with severe heart and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, and cerebral hemorrhage;
6. 2-3 grade hypertension or patients with poorly controlled hypertension;
7. Those with a history of mental illness that are difficult to control;
8. The investigator believes that it is not appropriate to participate in the trial;
9. Those who have been using immunosuppressive agents for a long time after organ transplantation, except for recent or current inhaled corticosteroids;
10. In the opinion of the investigator, the presence of medical history or mental state history or laboratory abnormalities may increase the risk associated with participating in the study or study drug administration, or may interfere with the interpretation of the results;
11. Screening indicates that the target cell transfection rate is less than 30%, or the T cell expansion is insufficient (less than 5 times) under CD3/CD28 stimulation conditions;
12. Unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events occurred 30 days or 30 days prior to grouping. If receiving anticoagulant therapy, the subject's therapeutic dose must be stable before grouping;
13. A subject who is pregnant or breastfeeding, or who is planning a pregnancy during or after 2 months of treatment;
14. Subjects who are women of childbearing age who are reluctant to receive high-efficiency contraception (according to institutional standards) during treatment and at least 2 months after the end of treatment. Female subjects of childbearing age are required to provide a negative result of a serum or urine pregnancy test within 48 hours prior to treatment;
15. There are active or uncontrollable infections requiring systemic treatment within 14 or 14 days prior to grouping;
16. Subjects who are unwilling or unable to comply with the research requirements.

Primary outcomes:
measure: To Determine the Maximum Tolerated Dose of TCR T-cell Therapy
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Universitty Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Hai Qiang Mai, MD,PhD
role: STUDY_CHAIR
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