sequential treatment of cd19 carnk and 7x19 car-t in r/r b cell lymphoma

Conditions: Primary Mediastinal B-cell Lymphoma (PMBCL); Mantle Cell Lymphoma (MCL); Diffuse Large B Cell Lymphoma( DLBCL)

Summary: to study the safety and efficacy of cord blood-derived cd19 car-nk cells sequential with 7x19 car-t in relapse / refractory b cell lymphoma

this is a single-center, open, single-arm clinical exploratory study to observe the safety and efficacy of cord blood derived cd19 car-nk cells sequential treatment with 7x19 car-t in relapse / refractory b cell lymphoma. this study consisted of two phases: phase i: carnk cells preparation and infusion (day0, dose of 2 x 10\^6 / kg). phase ii: 7x19 car-t cells preparation and infusion (day7, dose 2×10\^6/kg).

Eligibility criteria:
inclusion criteria: 1. age 18-75 years old, no gender limit; 2. 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: 1. 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 ； 2. refractory or relapsed mcl must be resistant to or intolerable to btk inhibitors; 3. refractory or relapsed indolent b-cell nhl is the failure or recurrence of third-line treatment; 3. previous treatment must include cd20 monoclonal antibody treatment (unless the subject is cd20 negative) and anthracyclines; 4. at least one measurable lesion with the longest diameter ≥ 1.5 cm exists; 5. the expected survival period is ≥12 weeks; 6. the puncture section of the tumor tissue was positive for cd19 expression; 7. ecog score 0-2 points; 8. sufficient organ function reserve: 1. alanine aminotransferase, aspartate aminotransferase ≤ 2.5× unl (upper limit of normal value); 2. creatinine clearance rate (cockcroft-gault method) ≥60 ml/min; 3. serum total bilirubin and alkaline phosphatase ≤1.5× unl; 4. glomerular filtration rate\&gt;50ml/min 5. cardiac ejection fraction (ef) ≥50%; 6. under natural indoor air environment, basic oxygen saturation\&gt;92% 9. allow a previous stem cell transplantation 10. 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; 11. allow patients who have previously received car-t cell therapy and have failed or relapsed after 3 months of evaluation; 12. female subjects of childbearing age must have a negative pregnancy test and agree to take effective contraceptive measures during the trial 13. two tests for the new coronavirus or swine flu virus are negative. exclusion criteria: 1. allergic to any of the components of cell products; 2. history of other tumors; 3. acute gvhd or extensive chronic gvhd with grade ii-iv (glucksberg standard) in the past or are receiving anti-gvhd treatment; 4. had received gene therapy within the past 3 months; 5. active infections requiring treatment (except for simple urinary tract infections, bacterial pharyngitis); however, prophylactic antibiotics, antiviral and antifungal infection treatment are permitted; 6. patents infected with hepatitis b (hbsag positive, but hbv-dna \&lt; 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 dysfunction according to the new york heart association\&#39;s cardiac function grading criteria; 8. patients who received antitumor therapy earlier but did not recover from the toxicity (ctcae 5.0 toxicity did not recover to ≤ grade 1, except fatigue, anorexia, alopecia); 9. subjects with a history of epilepsy or other central nervous system disorders; 10. head-enhanced ct or mri showing evidence of central nervous system lymphoma; 11. lactating women who are unwilling to stop breastfeeding; 12. any other factors that the investigator believes may increase the risk to the subject or interfere with the test results.