clinical study of cord blood-derived car nk cells targeting cd19/cd70 in refractory/relapsed b-cell non-hodgkin lymphoma

Conditions: B-cell Non Hodgkin Lymphoma

Summary: to study the safety and efficacy of cord blood-derived car-nk cells targeting cd19/cd70 in patients with b-cell non-hodgkin's lymphoma

this is a single-center, open, one-arm, dose-escalation study to observe the safety and efficacy of cord blood-derived dualcar-nk19/70 cells in patients with b-cell non-hodgkin lymphoma.9-18 patients are planned to be enrolled in the dose-escalation trial (2×10\^6 cells/kg, 4×10\^6 cells/kg, 8×10\^6 cells/kg) . each dose was given once a week for 3 weeks.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: 1. voluntarily participate in the study and sign the informed consent; 2. age 18-75, male and female; 3. histologically confirmed diffuse large b-cell lymphoma (dlbcl), transformed follicular lymphoma (tfl), primary mediastinal b-cell lymphoma (pmbcl), mantle cell lymphoma (mcl), and other inert b-cell nhl transforming types: (1)refractory or recurrent dlbcl and tfl must be approved by 2 line immune disease relapse after chemotherapy treatment; (2) refractory definition large b cell lymphoma (research scholar - 1 standard) : more than 4 courses first-line immune chemotherapy disease progression; the stable time of the disease is equal to or less than 6 months; or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation; (3) refractory or recurrent mcl must be 1 line with immune chemotherapy; btk inhibitors are resistant or intolerant as 2-line therapy; (4)always treatment must include cd20 single resistance (unless the subjects for cd20 negative) and anthracycline-based; 4. there was at least one measurable lesion with the longest diameter ≥1.5 cm; 5. predicted survival ≥12 weeks; 6. the expression of cd19 or cd70 in biopsy sections of tumor tissue was positive; 7. ecog score 0-2; 8. adequate reserve of organ functions: 1. cereal third transaminase, aspartate aminotransferase 2.5 x or less unl (upper limit of normal); 2. creatinine clearance (cockcroft - gault method) or 60 ml/min. 3. serum total bilirubin and alkaline phosphatase (1.5 x or less unl. 4. glomerular filtration rate \> 50 ml/min 5. heart ejection fraction (ef) 45% or higher; 6. indoor natural air environment, basic oxygen saturation \> 92% 7. blood routine: neutrophils absolute number \> 1000 cells/mm3, platelet count 45 x109, 8.0 g/dl hemoglobin; 9. allowed to have received a previous stem cell transplant 10. approved anti-b-cell lymphoma therapies, such as systemic chemotherapy, systemic radiotherapy and immunotherapy, had been completed for at least 3 weeks before the study. the eluting period of targeted drug regimens without chemotherapy was 2 weeks; 11. patients who had previously received car t cell therapy and failed to respond to a 3-month evaluation or relapsed were admitted; 12. female subjects of childbearing age must test negative for pregnancy and agree to use effective contraceptive methods during the trial 13. two tests have come back negative for covid-19. exclusion criteria: 1. allergic to any of the components of cell products; 2. history of other tumors; 3. acute gvhd or generalized chronic gvhd with grade ii-iv (glucksberg standard) after previous allogeneic hematopoietic stem cell transplantation; or being treated with anti-gvhd; 4. had received gene therapy in the past 3 months; 5. active infections requiring treatment (other than simple urinary tract infections and bacterial pharyngitis), however, prophylactic antibiotics, antiviral and antifungal infections are allowed; 6. subjects infected with hepatitis b (hbsag positive, but hbv-dna\<103 is not excluded) or hepatitis c virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to hiv-infected persons; 7. subjects with grade iii or iv cardiac insufficiency according to the new york heart association cardiac function grading criteria; 8. patients who received antitumor therapy in the early stage but the toxicity reaction did not recover (ctcae 5.0 toxicity reaction did not recover to ≤ level 1, except fatigue, anorexia and alopecia); 9. subjects with a history of epilepsy or other central nervous system diseases; 10. skull enhanced ct or mri showing evidence of central nervous system lymphoma; 11. lactating women who refuse to stop breastfeeding; 12. any other circumstances that the investigator believes may increase the subject's risk or interfere with the test results.