Safety and Efficacy
Conditions
Keywords
NKG2D CAR-NK, Relapsed or Refractory Acute Myeloid Leukemia
Brief 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.
Detailed description
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
Interventions
BIOLOGICALCAR-NK cells
NKG2DL-specific CAR-NK cells, 2 infusions on Day 0 and Day 7
Sponsors
Hangzhou Cheetah Cell Therapeutics Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity | 28 days | To evaluate the clinical safety and short-term efficacy of NKG2D ligand-specific umbilical cord blood CAR-NK cells in the treatment of patients with relapsed refractory acute myeloid leukemia by intravenous infusion |
| Maximal Tolerable Dose | 28 days | tolerability evaluationtransplantation after intravenous infusion of NKG2D ligand-specific umbilical cord blood CAR-NK cells for patients with relapsed refractory acute myeloid leukemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| leukemia-free survival#LFS# | 52weeks | leukemia-free survival |
Countries
China
Outcome results
None listed