Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory B-cell Malignancies

Exclusion Criteria

• •1. Known allergic reaction, hypersensitivity, intolerance or contraindication to CAR NK-CD19 or any component of drugs that may be used in the study (including fludarabine, cyclophosphamide and tozumab), or subjects who have had severe allergic reaction in the past;
• •2. Participants with gastrointestinal lymph nodes and / or central nervous system involvement who were judged by the researchers to be at risk by CAR NK-CD19 treatment (except those who were judged by the researchers to be more likely to benefit than risk);
• •3. Those who have graft-versus-host response and need to use immunosuppressants; or suffering from autoimmune diseases;
• •4. Before screening, the researchers judged that corticosteroids needed to receive a long-term therapeutic dose during the study period;
• •5. Received the following anti-tumor treatment within the specified time before screening:
• •i. Have received small molecule targeted therapy within 4 weeks or 5 half lives (whichever is longer); ii. Have received macromolecular drug treatment within 4 weeks or 2 half lives (whichever is longer); iii. Have received cytotoxic treatment or modern traditional Chinese medicine preparation with antitumor effect within 2 weeks;
• •6. Those who have been vaccinated with live vaccine or attenuated vaccine within 4 weeks before screening; Note: it is allowed to receive inactivated virus vaccine for seasonal influenza; However, it is not allowed to receive live attenuated influenza vaccine for intranasal use;
• •7. History of epilepsy or other central nervous system diseases;
• •8. Other active malignant tumors in the two years before screening (except for the following cases: tumors targeted in this study, surgically removed non-melanoma skin cancer, cured cervical carcinoma in situ, local prostate cancer, low-stage bladder cancer, breast ductal carcinoma in situ, or no recurrence and no treatment of malignant tumors in the two years before randomization);
• •9. Within 14 days before enrollment, there were active or uncontrollable infections requiring systemic treatment;
• •10. Active hepatitis B participants; Hepatitis C virus (HCV) antibody positive; Human immunodeficiency virus (HIV) antibody positive; Syphilis antibody positive in primary screening;
• •a) Participants with inactive / asymptomatic carrier, chronic or active HBV infection can be included if they meet the following conditions: HBV DNA \< 500 IU / ml (or 2500 copies / ml) at the time of screening.
• •11. The toxicity (including peripheral neuropathy) caused by previous treatment has not fully recovered or stabilized to grade 1 (nci-ctcae V5.0) (except those that the researcher judges will not affect the patient's safe treatment, such as hair loss);
• •12. Heart disease: there is heart failure (NYHA classification ≥ class II, Appendix 2) and serious heart disease determined by the researcher; Myocardial infarction occurred ≤ 6 months before screening; Unstable angina pectoris, severe arrhythmia judged by the researcher or coronary artery bypass grafting (CABG) occurred ≤ 3 months before screening;
• •13. Poor control of hypertension (systolic blood pressure \> 160 mmHg and / or diastolic blood pressure \> 100 mmHg) or accompanied by hypertensive crisis or hypertensive encephalopathy;
• •14. Participants who had undergone major surgery or plasma separation other than diagnosis or biopsy within 4 weeks before screening, or were expected to undergo major surgery during the study; Note: participants who plan to perform surgery under local anesthesia can participate in the study. Kyphoplasty or laminoplasty is not considered a major operation;
• •15. Those who are receiving thrombolytic, anticoagulant or antiplatelet therapy;
• •16. The subjects judged by the researcher are difficult to complete all visits or operations required by the study protocol, or the compliance of participating in the study is insufficient.