CD19-positive refractory and relapsed non-Hodgkin's lymphoma
Conditions
Interventions
Dose-escalation group:Gene-modified tumor infiltrating lymphocytes
Sponsors
Jiangsu Province Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 and = 45% ,with no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings, and no clinically significant pleural effusion; Baseline oxygen saturation > 91% on room air. Clinical laboratory examination indexes: (1) hematological examination indexes: no blood transfusion, no treatment with granulocyte colony stimulating factor (G-CSF) and no drug correction within 14 days before screening: A.Neutrophil count >= 1.0×10^9/L Lymphocyte count >= 0.3×10^9/L B. Hemoglobin >= 80 g/L; C. Platelet count >= 50×10^9/L (2) Biochemical indexes: A. total bilirubin (TBIL) = 3.0g/dl(3) Coagulation function: prothrombin time (PT) <= 1.5, upper limit of normal value (ULN); Activated partial prothrombin time (APTT) <= 1.5 upper limit of normal value (ULN)(4) Urine routine: urine protein concentration <= 1+ without edema; 8. Non-hematological toxicity caused by previous treatment (except disease-related) was restored to <= 1 before enrollment (except for hair loss and neurotoxicity <= 2 caused by chemotherapy drugs); 9. Eligible fertile patients (male and female) must agree to use reliable contraceptive methods (hormone or barrier method or abstinence, etc.) with their partners during the trial and at least 90 days after the last medication; The blood or urine pregnancy test of female patients of childbearing age within 7 days before the first use of the study drug must be negative; 10. Be able to follow the clinical research plan and follow-up process .Voluntarily participate in the clinical study and sign the informed consent.
Exclusion criteria
Exclusion criteria: 1. Active central nervous system (CNS) lymphoma (patients with symptoms of CNS disease must undergo lumbar puncture or MRI to exclude the diagnosis of CNS lymphoma); 2. Patients with active central nervous system diseases, such as seizures, cerebrovascular ischemia/hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, brain organic Syndrome, mental illness or any autoimmune disease involving the central nervous system; 3. Patients who received chemotherapy within 2 weeks before cell reinfusion, except for the following conditions: pretreatment chemotherapy as prescribed in the plan; bridging therapy sheath chemotherapy to prevent CNS lymphoma (must stop 1 week before infusion); 4. Received systemic glucocorticoid (prednisone > 10mg/day or equivalent dose of this type of drugs) or other immunosuppressants within 2 weeks before apheresis; Except for the following cases: short-term use of glucocorticoids for preventive treatment (e.g. prevention of contrast medium allergy); 5. Those who underwent autologous stem cell transplantation (ASCT) within 6 weeks before cell reinfusion; 6. Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT); 7. Any active autoimmune disease or history of autoimmune disease (such as, but not limited to, autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, systemic lupus erythematosus and rheumatoid arthritis, and asthma in which subjects need bronchodilators for medical intervention) cannot be included; However, the following patients were allowed to enter the group: vitiligo, psoriasis and hair loss without systemic treatment; Well controlled type I diabetes with replacement therapy, and hypothyroidism with normal thyroid function. 8. Hepatitis B: HBsAg (+) or HBeAg (+); Or anti-HBe (+)/anti-HBc (+), while HBV DNA was higher than that of the center. Hepatitis C: anti HCV positive; Treponema pallidum antibody (+)and RPR(+); HIV antibody test positive. 9. Have received major surgery within 4 weeks before screening, and the investigator has assessed that they are not suitable for inclusion; 10. Patients with active malignant tumors at the same time; patients with a history of malignant tumors and the disease has been cured for more than 2 years can be selected; 11. Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to: (1) have serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, ii-iii degree atrioventricular block, etc. (2) Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 and above cardiovascular events occurred within 6 months before the first administration. (3) New York Heart Association (NYHA) cardiac function grade = grade II or left ventricular , or structural heart disease with high risk judged by other researchers; (4) Clinically uncontrollable hypertension. 12. Lymphoma involving the atrium or ventricle; 13. During screening, there are clinical emergencies (such as intestinal obstruction or vascular compression) that require urgent treatment due to obstruction or compression of the lymphoma tumor; 14. Those who have a history of pulmonary embolism within 6 months before screening; 15. Those who are known to have a history of hypersensitivity to the ingredients of the preparation used in the study; 16. Live vaccine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity ;Maximum tolerated dose ;Best Overall Response; | — |
Secondary
| Measure | Time frame |
|---|---|
| overall survival, OS;overall response rate,ORR;Time to response,TTR;duration of response,DOR; | — |
Countries
China
Contacts
Public ContactJianyong Li
Jiangsu Province Hospital
Outcome results
None listed