NKG2D CAR-NK Cell Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- leukemia-free survival#LFS# [52weeks]
leukemia-free survival
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age: ≥ 10 years old and ≤ 75 years old, male or female;
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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;
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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;
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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;
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Physical status assessment (ECOG-PS) of the Eastern Oncology Collaborative Group is 0-2 points;
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Estimated survival > 3 months
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Flow cytometry check for NKG2D ligand expression on the surface of cancer cells for a reference of selecting patients
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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;
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The patient's peripheral superficial vein can meet the needs of intravenous injection;
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No other serious diseases that conflict with this protocol (e.g., autoimmune diseases, immunodeficiency, organ transplantation);
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No history of other malignant tumors;
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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;
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Subjects have negative HIV, HBV, HCV, syphilis serology test results
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Written informed consent form must be signed before enrollment.
Exclusion Criteria:
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Acute promyelocytic leukemia (type M3);
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Patients with cardiac insufficiency, patients with hepatic and renal insufficiency;
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Those who need treatment with other malignant tumors;
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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;
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Also suffering from other hematologic diseases (such as hemophilia, myelofibrosis, etc., which researchers consider unsuitable for inductees);
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Diffuse vascular internal coagulation;
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Concomitant serious infection or other serious underlying medical condition;
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Have immunodeficiency and autoimmune diseases;
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Have severe allergic diseases;
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Clinical symptoms of brain dysfunction or severe mental illness that can not understand or follow the research protocol;
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Have participated in clinical trials of other drugs within 4 weeks or within 21 days of surgery;
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Have received cell therapy in the previous 1 month;
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Have received hormonal drug therapy in the previous 14 days;
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Known HIV-positive patients or hepatitis B and C patients and syphilis patients;
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Have received organ transplants (excluding stem cell transplant patients);
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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;
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Pregnant or lactating women;
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Those who cannot be followed up as scheduled;
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Investigator considers that the subject has any clinical or laboratory abnormalities or compliance problems and is not suitable to participate in this clinical study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hebei Yanda Lu Daopei Hospital | Sanhe | Hebei | China |
Sponsors and Collaborators
- Hangzhou Cheetah Cell Therapeutics Co., Ltd
Investigators
- Principal Investigator: Peihua Lu, MD, Hebei Yanda Lu Daopei Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CARNK-001