Relapsed/refractory EBV positive lymphoma/nasopharyngeal carcinoma
Conditions
Interventions
Lymphoma Cohort (DL1):EBV CAR T cell therapy
Nasopharyngeal Cancer Cohort (DL2):EBV TCR-T cell therapy
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) Voluntarily signed written informed consent; 2) Aged >= 18 and = 3 months; 4) The Eastern Collaborative Cancer Organization (ECOG) physical condition score was 0-2 (Appendix 3); 5) Ebers (Eber-ish) was diagnosed as EBV-positive lymphoma (NK/T or T cell lymphoma, vascular immunoblastic T cell lymphoma, etc.) or nasopharyngeal carcinoma by in situ hybridization; 6) Pathological detection of wax block sections (within 1 year after diagnosis) : positive GP350 test in lymphoma patients, positive LMP2A and HLA classification in nasopharyngeal cancer patients: positive HLA-A*0201/2402/1101; 7) Subsubjects have at least one measurable lesion according to the Lugano Efficacy Evaluation Criterion (lymphoma) or Recist V1.1 Solid Tumor Evaluation Criterion (nasopharyngeal carcinoma); 8) Patients with relapsed/refractory lymphoma or nasopharyngeal cancer who have previously received second-line or above single drug or combination therapy failure or intolerance; 9) Venous access can be established for single collection or venous collection, and there are no other contraindications for blood cell separation; 10) Full organ and bone marrow function, defined as follows: A. Blood routine: neutrophils count (NEUT#) >= 1.0 x 10^9/L;Platelet count (PLT) >= 50 x 10^9/L (>= 80 x 10^9/L in patients with nasopharyngeal carcinoma); Hemoglobin concentration >= 70 g/L (>= 90g/L in patients with nasopharyngeal cancer); B. Liver function: AST and ALT = 50 mL/min; D. Coagulation function: International standardized ratio (INR) <= 1.5 x ULN and activated partial thromboplastin time (APTT) <= 1.5 x ULN; 11) Toxicity and side effects caused by early anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, etc.) <= 1 (CTCAE 5.0); 12) Fertile subjects (both male and female) shall be provided with effective medical contraceptives during the study period and within 6 months after the end of administration.For female subjects of reproductive age, a pregnancy test must be performed within 72 hours prior to the first administration of the drug and the result is negative.
Exclusion criteria
Exclusion criteria: 1) NK/T cell lymphoma patients with hemophilic cell syndrome; 2) Active central nervous system metastases (except those stabilized by treatment); 3) HIV-positive, HBsAg positive and HBV DNA copy number positive (quantitative detection >= 1000cps/ml, HCV antibody positive and HCV RNA positive; 4) People with mental or mental illness who cannot cooperate with treatment and efficacy evaluation; 5) Subjects with severe autoimmune diseases and long-term use of immunosuppressive agents; 6) Active or uncontrollable infections requiring systemic treatment during the 14 days before enrollment; 7) Any unstable systemic disease (including but not limited to): active infection (except local infection); Unstable angina pectoris; Cerebrovascular ischemia or cerebrovascular accident (within 6 months before screening); Myocardial infarction (within 6 months before screening); Congestive heart failure (New York Heart Association [NYHA] classification (see Appendix 4) >= III);Severe arrhythmias requiring medical treatment;Having heart disease requiring treatment or uncontrolled hypertension after treatment (blood pressure > 160 mmHg/100 mmHg); 8) Complicated with lung, brain, kidney and other important organ dysfunction; 9) Subjects had undergone major surgery or major trauma within 4 weeks prior to cell therapy, or were expected to undergo major surgery during the study period. 10) Subjects received their last radiotherapy or antitumor therapy (chemotherapy, targeted therapy, or immunotherapy) within 4 weeks prior to cell therapy 11) Subjects currently have or have had other malignant tumors that are incurable within 3 years, except for cervical cancer in situ or basal cell carcinoma of the skin, or other malignant tumors with disease-free survival over 5 years; 12) T cells (including CAR T and TCR-T) treated with chimeric antigen receptor (CAR T) within half a year; 13) Complicated with graft versus host disease (GVHD); 14) Subjects who were receiving systemic steroid therapy prior to screening and were determined by the investigator to require long-term systemic steroid therapy during the treatment period (other than inhalation or topical use);And subjects who received systemic steroid treatment within 72 h prior to cell reinfusion (except inhalation or topical use); 15) A history of severe allergies or allergies; 16) Subjects requiring anticoagulant therapy; 17) Pregnant or lactating women, or planning to become pregnant within six months (for both sexes); 18) Researchers believe that there are other reasons for not being included in treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity;maximal tolerated dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Amplification and persistence of EBV CAR-T/TCR-T cells in vivo;objective remission rate;progression free survival; | — |
Countries
China
Contacts
Public ContactYi Zhang
The First Affiliated Hospital of Zhengzhou University
Outcome results
None listed