Clinical trial NCT05247957: NKG2D CAR-NK Cell Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: NKG2D CAR-NK Cell Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Safety and Efficacy
Keywords: NKG2D CAR-NK
Relapsed or Refractory Acute Myeloid Leukemia
Lead sponsor: Hangzhou Cheetah Cell Therapeutics Co., Ltd
Sponsor class: OTHER
First posted: 2022-02-21
Enrollment: 9
Sex: ALL
Minimum age (years): 10
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Dose-Limiting Toxicity
timeFrame: 28 days
measure: Maximal Tolerable Dose
timeFrame: 28 days
Secondary outcomes:
measure: leukemia-free survival#LFS#
timeFrame: 52weeks
Other outcomes:
Locations:
city: Sanhe
country: China
facility: Hebei Yanda Lu Daopei Hospital
state: Hebei
Study officials:
affiliation: Hebei Yanda Lu Daopei Hospital
name: Peihua Lu, MD
role: PRINCIPAL_INVESTIGATOR
References: