CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL

Inclusion Criteria

• •Subjects must meet the following criteria for inclusion in the study： 1) Male or female subjects between the ages of 18 and 75（including critical values）； 2) Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell lymphoma (MCL) ：
• •a） Refractory B-NHL ：Subjects of which the best response to standard first-line treatment is PD,(those intolerant to first-line treatment will not be included in this study). Subjects of which the best response to at least four courses of first-line treatment is SD, with a duration of SD less than 6 months after the last treatment. Subjects of which the best response to the last course of second-line treatment or above treatments is PD or the best response to at least two courses of second-line treatment or above treatments is SD, with a duration of SD less than 6 months.
• •1. Male or female subjects between the ages of 18 and 75（including critical values）；
• •2. Subjects histologically confirmed as diffuse diffuse large B cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), primary mediastinal B cell lymphoma (PMBCL) and mantle cell lymphoma (MCL) ：
• •1. Refractory B-NHL ：Subjects of which the best response to standard first-line treatment is PD,(those intolerant to first-line treatment will not be included in this study). Subjects of which the best response to at least four courses of first-line treatment is SD, with a duration of SD less than 6 months after the last treatment. Subjects of which the best response to the last course of second-line treatment or above treatments is PD or the best response to at least two courses of second-line treatment or above treatments is SD, with a duration of SD less than 6 months.
• •2. Relapsed B-NHL：The disease relapses confirmed by histopathology in subjects who achieved complete remission after standard systematic treatment and second-line treatment. Or the disease relapses confirmed by histopathology within 1 year after hematopoietic stem cell transplantation (not limited to the previous therapeutic regimen) ；
• •3. Previous treatment must include CD20 monoclonal antibody (except patients with CD20 negative B cell NHL) and anthracycline；
• •4. Subjects with TFL must receive chemotherapy before transformation and meet the above definition of relapse or refractory after transformation.
• •3. According to Lugano response criteria 2014, there should be at least one evaluable tumor focus: the longest diameter of intranodal focus \> 1.5cm, the longest diameter of extranodal focus \> 1.0cm；
• •4. Positive expression of CD19 or CD22 in tumor tissue；
• •5. Subjects who have no effect or relapse after single-target CAR-T treatment can also be included in the group.
• •6. Approved anti-tumor therapies, such as systemic chemotherapy, systemic radiotherapy, and immunotherapy, have been completed for at least 2 weeks before the precondition.
• •7. ECOG≤1；
• •8. Life expectancy ≥ 3 months；
• •9. Neutrophil absolute count ≥ 1×10\^9/L；
• •10. platelet count ≥ 50×10\^9/L；
• •11. Absolute lymphocyte count ≥ 1×10\^8/L ；
• •12. Adequate organ function reserve :
• •1. GPT, GST ≤ 2.5× UNL（upper normal limit）；
• •2. Creatinine clearance (Cockcroft Gault method）≥60mL/min；
• •3. Serum total bilirubin ≤1.5× UNL；
• •4. The left ventricular ejection fraction (LVEF) ≥ 50% was diagnosed by echocardiography, and there was no clinically significant pericardial effusion and ECG abnormality；
• •5. Basic oxygen saturation in indoor natural air environment \> 92%；
• •13. It can establish the venous access needed for collection without the contraindications of leukocyte collection；
• •14. For female subjects of childbearing age, results are negative in urine pregnancy test before screening and administration, and subjects agree to take effective contraceptive measures at least one year after infusion; Male subjects with partners' fertility must agree to use effective barrier contraceptive methods at least one year after infusion, and avoid sperm donation；
• •15. Voluntary signing of informed consent;