nkg2d car-nk cell therapy in patients with relapsed or refractory acute myeloid leukemia

Conditions: Safety and Efficacy

Summary: this trial will explore the maximum tolerated dose of cord blood nkg2d car-nk in the treatment of recurrent refractory acute myeloid leukemia in a dose-escalation manner, and observe its clinical safety and efficacy.

this is a single arm, open-label, phase 1 study initiated with 3 cohorts: cohort 1: 2×10∧6/kg car-nk cells, 2 infusions on day 0 and day 7 cohort 2: 6×10∧6/kg car-nk cells, 2 infusions on day 0 and day 7 cohort 3: 18×10∧6/kg car-nk cells, 2 infusions on day 0 and day 7

Eligibility criteria:
inclusion criteria: 1. age: ≥ 10 years old and ≤ 75 years old, male or female; 2. meet the diagnostic criteria for recurrent aml: detection of leukemia cells after complete remission (cr) or \>0.1% of leukemia cells in bone marrow, including recurrence after allogeneic hematopoietic stem cell transplantation, or extramedullary infiltration of leukemia cells; 3. initial cases with failure of 2 lines of standard treatment; patients who relapsed within 12 months after consolidation intensification after cr; recurrence in 12 months and no respond to conventional chemotherapy; 2 or more recurrences; persistent extramedullarial leukemia; 4. patients currently have no effective treatment options, such as chemotherapy or allogeneic hematopoietic stem cell transplantation, or patients voluntarily choose to infuse nkg2d car-nk cells as the first treatment option; 5. physical status assessment (ecog-ps) of the eastern oncology collaborative group is 0-2 points; 6. estimated survival \> 3 months 7. flow cytometry check for nkg2d ligand expression on the surface of cancer cells for a reference of selecting patients 8. the main organs of the patient are well functioned: (1) cardiac function: no heart disease or coronary heart disease, the patient's cardiac function grade 1-2; (2) liver function: tbil≦3uln, ast≦2.5uln, alt≦2.5uln; (3) renal function: cr≦1.25uln; 9. the patient's peripheral superficial vein can meet the needs of intravenous injection; 10. no other serious diseases that conflict with this protocol (e.g., autoimmune diseases, immunodeficiency, organ transplantation); 11. no history of other malignant tumors; 12. women of childbearing age must be tested negative for pregnancy within 7 days, and subjects of childbearing age must use appropriate contraception during both the trial and for 3 months after the test; 13. subjects have negative hiv, hbv, hcv, syphilis serology test results 14. written informed consent form must be signed before enrollment. exclusion criteria: 1. acute promyelocytic leukemia (type m3); 2. patients with cardiac insufficiency, patients with hepatic and renal insufficiency; 3. those who need treatment with other malignant tumors; 4. poorly controlled hypertension (systolic blood pressure \>160 mmhg and/or diastolic blood pressure \>90 mmhg) or clinically significant cardiovascular and cerebrovascular diseases such as cerebrovascular accident (within 6 months before signing the informed consent form), myocardial infarction (within 6 months before signing the informed consent), unstable angina, congestive heart failure, or severe arrhythmias that cannot be controlled with drugs or have a potential impact on research treatment; 5. also suffering from other hematologic diseases (such as hemophilia, myelofibrosis, etc., which researchers consider unsuitable for inductees); 6. diffuse vascular internal coagulation; 7. concomitant serious infection or other serious underlying medical condition; 8. have immunodeficiency and autoimmune diseases; 9. have severe allergic diseases; 10. clinical symptoms of brain dysfunction or severe mental illness that can not understand or follow the research protocol; 11. have participated in clinical trials of other drugs within 4 weeks or within 21 days of surgery; 12. have received cell therapy in the previous 1 month; 13. have received hormonal drug therapy in the previous 14 days; 14. known hiv-positive patients or hepatitis b and c patients and syphilis patients; 15. have received organ transplants (excluding stem cell transplant patients); 16. drug abuse, medical, psychological or social conditions that may interfere with a subject's participation in the study or evaluation of the results of the study; 17. pregnant or lactating women; 18. those who cannot be followed up as scheduled; 19. investigator considers that the subject has any clinical or laboratory abnormalities or compliance problems and is not suitable to participate in this clinical study.

Keywords: nkg2d car-nk relapsed or refractory acute myeloid leukemia