CD19-positive refractory and relapsed non-Hodgkin's lymphoma
Conditions
Interventions
Dose-escalation group (0.5x10^6/kg):Gene-modified tumor infiltrating lymphocytes
Dose-escalation group (3.3x10^6/kg):Gene-modified tumor infiltrating lymphocytes
Dose-escalation group (10x10^6/kg):Gene-modified tumor infiltrating lymphocytes
Sponsors
Jiangsu Province Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1.Age >= 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: 1)Neutrophil count >= 1.0×10^9/L Lymphocyte count >= 0.3×10^9/L; 2)Hemoglobin >= 80 g/L; 3)Platelet count >= 50×10^9/L; (2)Biochemical indexes: 1)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 CNS disease symptoms must undergo lumbar puncture and MRI to exclude CNS lymphoma); 2.Patients with current or history of central nervous system diseases, such as epilepsy, cerebral vascular ischemia / hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, brain organic syndrome, mental disease or any autoimmune disease involving the central nervous system; 3.Patients who received chemotherapy within 2 weeks before cell reinfusion, except for the following cases: pretreatment chemotherapy according to the protocol; In order to prevent CNS lymphoma, intrathecal chemotherapy (must be stopped 1 week before infusion); 4.Received systemic glucocorticoid (prednisone > 10 mg/day or equivalent dose of similar drugs) or other immunosuppressants within 14 days before apheresis; Except for the following cases: local, eye, intra-articular, intranasal and inhaled glucocorticoids; Short term use of glucocorticoids for preventive treatment (e.g. prevention of contrast medium allergy); 5.Autologous stem cell transplantation (ASCT) within 6 weeks before cell reinfusion; 6.Patients who had previously received allogeneic hematopoietic stem cell transplantation (allo HSCT); 7.Patients are known to have systemic vasculitis (e.g. Wegener granuloma, nodular polyarteritis), systemic lupus erythematosus, active or uncontrolled autoimmune diseases (e.g. Crohns disease, rheumatoid arthritis, autoimmune hemolytic anemia, autoimmune hepatitis, etc.) Primary or secondary immunodeficiency (such as HIV infection or severe infectious diseases); 8.Active viral infection. Hepatitis serological test is required during screening: (1)If hepatitis B surface antigen (HBsAg) is positive (HBV-DNA copy number > 10^4), the subject should be excluded; (2)If the subject's hepatitis B core antibody (HBcAb) is positive and the DNA is positive before enrollment, the subject should be excluded; (3)If hepatitis C antibody is positive, rnapcr test shall be carried out, and the results before enrollment shall be confirmed to be positive, and the subjects shall be excluded; (4)If the EBV antibody is positive and the copy number of EBV-DNA before enrollment is > 10^4, the subjects should be excluded; (5)If the CMV antibody is positive and the copy number of cmv-dna before enrollment is > 10^4, the subjects should be excluded; 9.Major surgery was performed within 4 weeks before screening, which was not suitable for inclusion after the evaluation of the researcher; 10.The patient had active malignant tumor at the same time; Patients with a history of malignant tumor and the disease has been cured for >= 2 years can be selected; 11.The patient's heart meets any of the following conditions: New York Heart Association (NYHA) grade III or IV congestive heart failure; Serious arrhythmias requiring treatment, including QTc interval >= 450ms for men and >= 470ms for women (qtcb = QT/rr1/2); Uncontrolled hypertension (systolic blood pressure >= 140mmHg and / or diastolic blood pressure >= 90mmHg) or pulmonary hypertension or unstable angina pectoris; Had myocardial infarction or bypass or stent surgery within 12 months before administration; Clinically significant valvular disease; Other heart diseases judged by the researcher as unsuitable for inclusion; 12.Lymphoma involving atrium or ventricle; 13.When screening, there are clinical emergencies that need urgent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity;Maximum tolerated dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival after drug administration;Objective response rate;Time to response;Best overall response;Duration of response; | — |
Countries
China
Contacts
Public ContactJianyong Li
Jiangsu Province Hospital
Outcome results
None listed