A Clinical Study to Evaluate the Safety, Tolerability and Initial Efficacy of Targeted Haploidentical Neoantigen T Cell Injection (hNeo-T) in the Treatment of Relapsed or Refractory EBV-positive T-cell Lymphoma
Objective: To evaluate the safety and tolerability of hNeo-T injection in patients with relapsed or refractory EBV-positive T-cell lymphoma. Secondary objective: To evaluate the effectiveness of hNeo-T injection, and to evaluate the objective response rate (ORR) and disease control rate (DCR) by Lugano2014 criteria; Progression-free survival (PFS), duration of response (DOR), and overall survival (OS ) followed. Objective of the exploratory study: To investigate the in vivo process of hNeo-T injection and describe the activity and related biological functions of hNeo-T cells in vivo, including but not limited to.
• Age ≥18 years old, and ≤75 years old, gender is not limited;
• Must have histologically or cytologically confirmed T-cell lymphoma with at least one measurable tumor lesion (according to Lugano2014 criteria);
• The subject's HLA type is HLA-A0201/1101/2402/0203 (containing at least one of the subtypes, as determined by the test report issued by the central laboratory), and there is at least one healthy donor who is a semi-matching HLA type or more with the subject. At least one of the HLA matching loci is HLA-A0201/1101/2402/0203;
• The subject has been previously determined to be EBV positive or has been determined to be EBV positive after testing;
• The subject has paraffin-embedded tumor tissue/section or biopsy tumor tissue within 2.5 years (tissue biopsy is recommended for subjects with easy-to-sample tumor lesions and consent to biopsy), and these tissues are qualified by gene sequencing data. And the tumor neoantigen screening qualified;
• Disease progression after adequate first-line systemic treatment, or disease progression ≥2 cycles (PD) after first-line or above systemic systemic treatment, or ≥4 cycles without remission (CR or PR). Remarks: The first-line systemic treatment should refer to the latest version of the Lymphoma Diagnosis and Treatment Guide issued by China's Chinese Society of Clinical Oncology.
• Volunteer to participate in clinical studies; I or legal guardian fully understand and know the study and sign the informed consent; Willing to follow and be able to complete all test procedures;
• ECOG score ≤1 score;
• Have venous access to meet venous blood collection;
⁃ The survival time is expected to be ≥6 months;
⁃ The subjects are willing to use a reliable method of contraception during treatment and within 3 months after the end of treatment, and the blood pregnancy test of women of childbearing age is negative;
⁃ Laboratory test results and vital organ functions meet the following requirements: 1) \*HIV antibody negative; No active syphilis infection; Negative antibodies to hepatitis C virus; HBV DNA detection value is lower than the upper limit of normal value; 2) Blood routine: absolute value of neutrophil (ANC) ≥1×10\^9/L, platelet count (PLT) ≥75×10\^9/L, hemoglobin concentration (HGB) ≥80g/L; 3) Blood biochemistry: glutamic-pyruvic transaminase (ALT) and glutamic-oxalic transaminase (AST) ≤3 times the upper limit of normal (ULN) (ALT and AST≤5 times ULN in liver metastasis subjects); Serum creatinine ≤1.5 ULN; Total bilirubin ≤1.5 ULN, or total bilirubin \<3 ULN for subjects with GilbertsSyndrome; 4) Coagulation function: prothrombin time (PT) and International standard ratio (INR) ≤1.5 times ULN, activated partial thromboplastin time (APTT) ≤1.5 times ULN (for subjects taking anticoagulant drugs for a long time, the coagulation related indexes can meet the normal value range after medication); 5) Left ventricular ejection fraction (LVEF) ≥50%;
⁃ Before administration with Chemotherapy preconditioning: 1) Any chemotherapy, targeted drugs, immune checkpoint inhibitors, other drugs studied in clinical trials, Chinese medicines with anti-tumor indications, and other anti-tumor treatments received have passed the 4-week washout period, and the toxic side effects have returned to grade 1 or lower (excluding hair loss, vitiligo, and other events that the investigator has judged to be tolerated); 2) If major surgery is performed within 3 weeks, adverse reactions have recovered to grade 1 or lower.