NKG2D CAR-NK Cell Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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
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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

Official Title
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NKG2D CAR-NK Cell Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Conditions
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Safety and Efficacy

Intervention / Treatment
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* Biological: CAR-NK cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: ≥ 10 years old and ≤ 75 years old, male or female; 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; 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; 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; Physical status assessment (ECOG-PS) of the Eastern Oncology Collaborative Group is 0-2 points; Estimated survival > 3 months Flow cytometry check for NKG2D ligand expression on the surface of cancer cells for a reference of selecting patients 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; The patient's peripheral superficial vein can meet the needs of intravenous injection; No other serious diseases that conflict with this protocol (e.g., autoimmune diseases, immunodeficiency, organ transplantation); No history of other malignant tumors; 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; Subjects have negative HIV, HBV, HCV, syphilis serology test results Written informed consent form must be signed before enrollment. Exclusion Criteria: Acute promyelocytic leukemia (type M3); Patients with cardiac insufficiency, patients with hepatic and renal insufficiency; Those who need treatment with other malignant tumors; 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; Also suffering from other hematologic diseases (such as hemophilia, myelofibrosis, etc., which researchers consider unsuitable for inductees); Diffuse vascular internal coagulation; Concomitant serious infection or other serious underlying medical condition; Have immunodeficiency and autoimmune diseases; Have severe allergic diseases; Clinical symptoms of brain dysfunction or severe mental illness that can not understand or follow the research protocol; Have participated in clinical trials of other drugs within 4 weeks or within 21 days of surgery; Have received cell therapy in the previous 1 month; Have received hormonal drug therapy in the previous 14 days; Known HIV-positive patients or hepatitis B and C patients and syphilis patients; Have received organ transplants (excluding stem cell transplant patients); 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; Pregnant or lactating women; Those who cannot be followed up as scheduled; Investigator considers that the subject has any clinical or laboratory abnormalities or compliance problems and is not suitable to participate in this clinical study.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NKG2DL-specific CAR-NK cells<br>Experimental: NKG2DL-specific CAR-NK cells, 2 infusions on Day 0 and Day 7 After preconditioning with chemotherapy, NKG2DL-specific CAR-NK cells will be evaluated | Biological: CAR-NK cells<br>* NKG2DL-specific CAR-NK cells, 2 infusions on Day 0 and Day 7<br>* Other names: NKG2DL-specific CAR-NK cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicity | 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 | 28 days | 
| Maximal Tolerable Dose | tolerability evaluationtransplantation after intravenous infusion of NKG2D ligand-specific umbilical cord blood CAR-NK cells for patients with relapsed refractory acute myeloid leukemia | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| leukemia-free survival#LFS# | leukemia-free survival | 52weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NKG2D CAR-NK, Relapsed or Refractory Acute Myeloid Leukemia