Acute Myeloid Leukemia
Conditions
Interventions
Experimental Group:Infusion of NKG2D-CAR-NK cells
Sponsors
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Patients or their legal guardians voluntarily participate and sign informed consent; 2. Male or female patients aged 18 to 70 years (including 18 and 70 years) need an HLA matched donor allo-HSCT; 3. High-risk acute myeloid leukemia (AML) is defined as having at least one of the following high risk characteristics: (1) meeting the cytogenetic/molecular genetic high risk stratification in the Chinese Guidelines for Adult AML Diagnosis and Treatment (2021 edition); (2) Initial treatment cases that failed after 2 courses of treatment with standard protocols; (3) Patients with recurrence within 12 months after CR consolidation and intensive treatment; (4) recurrences after 12 months but is ineffective after conventional chemotherapy; (5) two or more relapses; (6) extramedullary leukemia persisted; (7) Secondary AML; 4. Patients have available donors or sufficient cryopreserved donor-derived peripheral blood mononuclear cells (PBMC) for CAR-NK preparation. 5. NKG2D ligand expression on the surface of leukemia cells must be detected by immunohistochemistry or flow cytometry 6. The patient's main tissues and organs function well: (1) Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin =34.2µmol/L; (2) Renal function: creatinine < 220µmol/L; (3) Lung function: indoor oxygen saturation =90%; (4) Cardiac function: left ventricular ejection fraction (LVEF) =40%. 7. The patient's peripheral shallow vein blood flow is smooth, which can meet the needs of intravenous infusion; 8. Patients with ECOG score <2 and expected survival time =3 months. 9. After discussion by the expert group, the patient's condition was analyzed, and combined with the patient's general physical condition, the benefits of participating in clinical trials outweigh the risks;
Exclusion criteria
Exclusion criteria: 1. Acute promyelocytic leukemia and its variants; 2. Have been diagnosed with or treated for a malignancy other than AML within the 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer; Local prostate cancer or ductal carcinoma in situ after radical treatment; 3. The presence of central nervous system diseases, defined as cerebrospinal cord original cells detectable in cerebrospinal fluid samples, = 5 white blood cells per square millimeter; History or presence of any central nervous system disease, such as epilepsy, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system. 4. Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding; 5. Men or women who have plans to become pregnant within the last 1 year; 6. Patients are not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment; 7. Severe concurrent infection: Patients with concurrent bacterial infection must receive radical treatment and have no signs of infection progression within 72 hours prior to enrollment. For fungal infections, patients must receive thorough systemic antifungal therapy and have no signs of infection progression during the 1 week prior to enrollment. Progressive infection is defined as hemodynamic instability due to sepsis or new symptoms, worsening of signs due to infection, or radiological findings. A persistent fever without other signs or symptoms will not be interpreted as a progressive infection. ; 8. Active hepatitis B/C virus; 9. Hiv-infected patients; 10. Has a serious autoimmune disease; 11. The patient is allergic to macromolecular biological drugs such as antibodies or cytokines; 12. The patient had participated in other clinical trials within 6 weeks prior to enrollment; 13. Currently taking corticosteroids to treat GVHD, the dose is >0.5mg/kg prednisone. 14. GVHD evidence > Level II. ; 15. Persons with alcohol dependence, drug abuse and mental disorders; 16. Patients who have received a donor lymphocyte infusion within 28 days. 17. The patient has other medical or psychological conditions that are not suitable for CAR-NK cell immunotherapy 18. According to the investigator's judgment, the patient had other conditions that were not suitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Types and incidence of dose limiting toxicity (DLT);Adverse event (AE) incidence and severity; | — |
Secondary
| Measure | Time frame |
|---|---|
| Recurrence free survival(RFS);objective response rate(ORR);Progression-Free Survival(PFS); | — |
Countries
China
Contacts
Public ContactYicheng Zhang
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Outcome results
None listed