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

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.

Study Overview

• Status: Terminated
• Conditions: Safety and Efficacy
• Intervention / Treatment: Biological: CAR-NK cells

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

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hebei
    • Sanhe, Hebei, China
      • Hebei Yanda Lu Daopei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NKG2DL-specific CAR-NK cells; 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; NKG2DL-specific CAR-NK cells, 2 infusions on Day 0 and Day 7; Other Names: NKG2DL-specific CAR-NK cells

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hangzhou Cheetah Cell Therapeutics Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2021
• Primary Completion (Actual): December 12, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Relapsed or Refractory Acute Myeloid Leukemia; NKG2D CAR-NK
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: CARNK-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No