Natural Killer(NK) Cell Therapy Targeting CLL1 in Acute Myeloid Leukemia

Acute myelogenous leukemia (AML) is a potentially cur-able disease; 70% of newly diagnosed patients achievecomplete remission with first-line therapy, but prognosisworsens for relapsed disease in both pediatric and adultpatients. CLL-1 has attracted the researchers' attention due to its high expression in AML while being absent in normal hematopoietic stem cell. Accumulating evidence have demonstrated CLL-1 is an ideal target for AML.

Inclusion criteria

• ≥18 years old.
• Confirmed diagnosis of r/r AML
• CLL1 expression is positive in AML blasts.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 and life expectancy greater than 12 weeks.
• Adequate organ and marrow function, as defined below:

• Blood creatinine (Cr) ≤ 2 x ULN or calculated creatinine clearance (Cockcroft- Gault formula) ≥ 50 mL/min;
• Total bilirubin (TBIL) ≤ 2 x the ULN;
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN;
• International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
• Females of childbearing potential must have a negative serum pregnancy test.
• Donor specific antibody (DSA) is negative: MFI <= 2000.
• Provision of signed and dated informed consent form (ICF).

Exclusion criteria

• Allergic to drug used in this study.
• Subjects received any antitumor therapy as follows, prior to first NK infusion:

• Systemic steroid therapy within 3 days (except physiological replacement therapy);
• Systemic antitumor therapy within 2 weeks or at least 5 half-lives, whichever is less;
• Radiotherapy within 4 weeks;
• Donor lymphocyte infusion within 6 weeks;
• Intrathecal treatment within 1 week;
• CAR-T therapy, CAR-NK therapy, or any other genetically modified cell therapy product within 6 months;
• History of allogeneic stem cell transplantation.
• Received the vaccine within 4 weeks prior to the first infusion and/or expected to require vaccination from the study period to 12 weeks after the last infusion.
• Active central nervous system Leukemia.
• Acute Promyelocytic Leukemia (APL).
• History of other malignant tumors, except for those who have achieved complete remission more than 5 years after radical treatment without any signs of recurrence.
• Active autoimmune diseases.
• History of central nervous system disease or meningeal involvement such as epilepsy, paralysis, aphasia, stroke, etc.
• Serious cardiovascular and cerebrovascular diseases:

• Severe heart rhythm or conduction abnormalities, corrected QT interval (QTc)≥480 ms;
• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to first infusion;
• New York Heart Association (NYHA) class II or above congestive heart failure or left ventricular ejection fraction (LVEF) <50% in color Doppler echocardiography;
• Hypertension that cannot be controlled by drug.
• Active pulmonary infection; SpO2 ≤90%; Pulmonary embolism, chronic obstructive pulmonary disease, or interstitial lung disease.
• Uncontrolled bacterial, fungal, or viral infection. Known HIV infection, active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
• History of substance abuse.
• Toxicity induced by previous therapy not recovered to ≤ grade 2(NCI-CTCAE v5.0).
• Large surgical treatment within 4 weeks prior to first infusion, not including diagnostic biopsy.
• Pregnant/breastfeeding women.
• Investigator-assessed presence of any medical or social issues that are likely to interfere with study conduct or may cause increased risk to subject.