clinical study of cord blood-derived car-nk cells targeting cd19 in the treatment of refractory/relapsed b-cell nhl

Conditions: B-cell Non Hodgkin Lymphoma

Summary: to study the safety and effectiveness of cord blood-derived car-nk cells targeting cd19 in patients with b-cell non-hodgkin's lymphoma

this is an open, single-arm, single-dose, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of cb car-nk019 cells. 9-18 patients are planned to be enrolled in the dose-escalation trial (2×10\^6 cells/kg ,3×10\^6 cells/kg, 4×10\^6 cells/kg) . the primary endpoints are dlt, mtd, and the second endpionts are the overall response rates (cr and pr), overall survival, and progression-free survival. based on the results in the dose-escalation trial, the recommended dose will be determined. another 30 patients will be enrolled to estimate the safety and efficacy of cb car-nk019 under the best dose.

Eligibility criteria:
inclusion criteria: * inclusion criteria: volunteer to participate in this study and sign an informed consent form; age 18-75 years old, no gender limit; histologically diagnosed as diffuse large b-cell lymphoma (dlbcl), transforming follicular lymphoma (tfl), primary mediastinal b-cell lymphoma (pmbcl), mantle cell lymphoma (mcl) and other inert b-cells nhl conversion type: refractory or relapsed dlbcl refers to the failure to achieve complete remission after 2-line treatment; disease progression during any treatment, or disease stable time equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation ； refractory or relapsed mcl must be resistant to or intolerable to btk inhibitors; refractory or relapsed indolent b-cell nhl is the failure or recurrence of third-line treatment; previous treatment must include cd20 monoclonal antibody treatment (unless the subject is cd20 negative) and anthracyclines; at least one measurable lesion with the longest diameter ≥ 1.5 cm exists; the expected survival period is ≥12 weeks; the puncture section of the tumor tissue was positive for cd19 expression; ecog score 0-2 points; sufficient organ function reserve: alanine aminotransferase, aspartate aminotransferase ≤ 2.5× unl (upper limit of normal value); creatinine clearance rate (cockcroft-gault method) ≥60 ml/min; serum total bilirubin and alkaline phosphatase ≤1.5× unl; glomerular filtration rate\>50ml/min cardiac ejection fraction (ef) ≥50%; under natural indoor air environment, basic oxygen saturation\>92% allow a previous stem cell transplantation the approved anti-b-cell lymphoma treatments, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 3 weeks before the study medication; allow patients who have previously received car-t cell therapy and have failed or relapsed after 3 months of evaluation; female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial two tests for the new coronavirus were negative. exclusion criteria: * those who have a history of allergies to any of the ingredients in cell products; history of other tumors previously presented with ii-iv degree (glucksberg criteria) acute gvhd or extensive chronic gvhd; or are receiving anti-gvhd treatment; have received gene therapy in the past 3 months; active infections that require treatment (except for simple urinary tract infections and bacterial pharyngitis), but preventive antibiotics, antiviral and antifungal infection treatments are allowed; hepatitis b (hbsag positive, but hbv-dna \<103 is not an exclusion criterion) or hepatitis c virus infection (including virus carriers), syphilis and other subjects with acquired and congenital immunodeficiency diseases, including but not limited to people living with hiv; according to the new york heart association's heart function classification standard, it is classified as grade iii or grade iv. impaired subjects; those who have received anti-tumor therapy in the early stage but the toxic reaction has not recovered (the ctcae 5.0 toxic reaction has not recovered to ≤1, except for fatigue, anorexia, and hair loss); subjects with a history of epilepsy or other central nervous system diseases; enhanced ct or mri of the head showed evidence of central nervous system lymphoma; have received any other drugs that target cd19; women who are breastfeeding and unwilling to stop breastfeeding; any other situation that the investigator believes may increase the risk of the subject or interfere with the results of the test.