CD19-positive refractory relapsed non-Hodgkin's lymphoma
Conditions
Interventions
dose extension group:Based on the results of the dose escalation test, the recommended dose for the extension phase is determined
group 1:Chemotherapy pretreatment +ECAR-T (1x10^6)
group 2:Chemotherapy pretreatment +ECAR-T (3.3x10^6)
group 3:Chemotherapy pretreatment +ECAR-T (10x10^6)
group 4:Chemotherapy preconditioning+Toripalimab+ECAR-T (3.3x10^6)
group 5:Chemotherapy preconditioning+Toripalimab+ECAR-T (10x10^6)
Sponsors
The First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-70 years, regardless of gender; 2. Expected natural survival >=3 months; 3. Patients with CD19-positive invasive NHL WHO met the 2016 WHO classification, who received at least two or more lines of therapy including rituximab or other CD20-targeting drugs (except for CD20-negative tumors) and at least one anthracycline, who relapsed or were refractory, including those who relapsed after autohematopoietic stem cell transplantation, patients who are not currently eligible for standard treatment, or patients who refuse to accept conventional treatment options; 4. Voluntarily received peripheral blood monocytes for cell preparation, and PD1-positive T cells in peripheral blood accounted for more than 18% of total T cells. (Standard for BD Accuri C6 flow cytometer); 5. The Eastern Oncology Consortium (ECOG) physical status score was 0 to 1; 6. No serious hematological, hepatorenal function abnormalities, cardiac ejection fraction (LVEF) >= 45%, no obvious pericardial effusion found in cardiac Doppler examination, no clinically significant electrocardiogram abnormalities; No clinically significant pleural effusion; A minimum level of lung reserve, defined as 91% in non-oxygen state, meeting the following laboratory test results: (1) Blood system (no blood transfusion or hematopoietic stimulating factor treatment within 14 days) : neutrophil count (ANC) >=1.0x10^9/L, platelet (PLT) >=50x10^9/L, hemoglobin (Hb) >=80g/L, lymphocyte count (LYM) >=0.3x10^9/L; (2) Liver function (abnormal liver function caused by tumor infiltration ALT and AST =3.0g/dL; (3) Renal function: creatinine =60 mL/min (Cockcroft and Gault formula); (4) Blood coagulation function meets the requirements of activated partial thrombin time (APTT) <=1.5xULN, International normalized ratio (INR <=1.5xULN; (5) Urine routine: urine protein concentration <=1+, no edema; 7. Non-hematological toxic reactions caused by previous treatment (except disease-related) recovered to <= grade 1 before enrollment (except hair loss and <= grade 2 neurotoxicity caused by chemotherapy drugs); 8. Eligible patients who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence, etc.) with their partner during the trial period and for at least 90 days after the last medication; Blood or urine pregnancy tests must be negative for women of reproductive age (women within 1 year from menarche to menopause) within 7 days prior to first use of the study drug; 9. Patients must be informed of the study prior to the study, be able to follow the clinical study protocol and follow-up procedures, and voluntarily sign a written informed consent.
Exclusion criteria
Exclusion criteria: 1. Active central nervous system (CNS) lymphoma (patients with CNS disease symptoms must undergo a lumbar puncture or MRI to rule out active CNS lymphoma); 2. Patients with a history of active or present central nervous system diseases, such as seizures, cerebrovascular ischemia/bleeding, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, mental illness, or any autoimmune disease involving the central nervous system; 3. Patients who received chemotherapy within 2 weeks before cell retransfusion; The following conditions were excluded: pretreatment chemotherapy as prescribed by the protocol; Bridging therapy; Sheath chemotherapy for the prevention of CNS lymphoma (must be stopped 1 week before infusion); 4. Received systemic glucocorticoid (prednisone > 10mg/ day or equivalent dose of the same drug) or other immunosuppressant therapy within 2 weeks of monocarvest; Except in the following cases: treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; Short-term use of glucocorticoids for preventive treatment (e.g. to prevent hypersensitivity to contrast media); 5. Patients are known to have active systemic vasculitis (e.g., Wegener granuloma, polyarteritis nodosa), systemic lupus erythematosus, co-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 serious infectious diseases); 6. Hepatitis B: HBsAg(+); Or anti-HBe (+)/ anti-HBc (+) hepatitis B DNA quantity was higher than the upper limit of detection center; Hepatitis C: anti-HCV positive; Treponema pallidum antibody (+) and syphilis RPR test were positive. HIV antibody test positive; 7. Uncontrolled active infections (such as sepsis, bacteremia, fungemia, viremia, etc.) at the time of screening; 8. The patient also had active malignant tumors; Patients with a history of malignant tumor who have been cured for more than 2 years can be enrolled; 9. The patient's heart meets any of the following criteria: New York Heart Association (NYHA) Class III or IV congestive heart failure; Severe arrhythmias requiring treatment, including QTc interval >=450ms in men and >=470ms in women (QTcB=QT/RR1/2); Uncontrolled hypertension (systolic blood pressure >= 140mmHg and/or diastolic blood pressure >= 90mmHg) or pulmonary hypertension or unstable angina; Had myocardial infarction or bypass or stent surgery within 12 months prior to administration; Valvular disease of clinical significance; Other heart conditions that the researchers judged unsuitable for inclusion; 10. Lymphoma involving atrium or ventricle; 11. There are clinical emergencies (such as intestinal obstruction or vascular compression, etc.) that need urgent treatment due to lymphoma tumor obstruction or compression during screening; 12. A known history of hypersensitivity to the ingredients of the preparation used in the test; 13. Patients who have received allogeneic hematopoietic stem cell transplantation (allo-HSCT); Or patients who have received CAR T cell therapy; 14. Those who underwent autologous stem cell transplantation (ASCT) within 4 weeks prior to screening; 15. Had received major surgery within 4 weeks prior to screening and was assessed by the researchers as not suitable for inclusion; 16. Received other investigational drugs or treatments that are n
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Limiting Toxicity, DLT;Maximum Tolerated Dose, MTD; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival, OS;Duration of Response, DoR;Progression-Free Survival, PFS;Best Overall Response;Time-to-Response, TTR;Objective Response Rate, ORR; | — |
Countries
China
Contacts
Public ContactZhang Yi
Outcome results
None listed