Clinical Trial of CD123-targeted CAR-NK Therapy for Relapse/refractory AML or BPDCN

This study is a single-arm, open-label, dose-finding and expansion clinical trial aimed at evaluating the safety and efficacy of antiCD123 CAR-NK therapy for the treatment of patients with relapsed/refractory AML or BPDCN. The goal is to determine the recommended dose of CAR-NK cell therapy for these conditions. The study includes three dose groups: 1×107 CAR-positive cells/kg, 3×107 CAR-positive cells/kg, and 5×107 CAR-positive cells/kg. Each patient will receive two infusions of CAR-NK cells on D0 and D7, respectively, with the doses for both infusions principally remaining the same. However, the investigaors have the flexibility to adjust the second infusion dose based on the subject's condition.

Inclusion criteria

• Patients of any gender, aged between 18 and 75 years (inclusive);
• Positive expression of CD123 on tumor cells detected by flow cytometry;
• Patients with a confirmed diagnosis of CD123-positive relapsed/refractory AML or BPDCN:

(1) For AML patients：

• Relapsed refers to the reappearance of leukemic cells in peripheral blood after complete remission (CR), or ≥5% blasts in bone marrow (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy), or the presence of leukemic cell infiltration outside the marrow;
• Refractory refers to patients who have not responded to two courses of standard treatment; patients who have relapsed within 12 months after CR and consolidation/intensification therapy; patients who have relapsed after 12 months but have not responded to conventional chemotherapy; patients with two or more relapses; patients with persistent extramedullary leukemia;

(2) For BPDCN patients: Patients who have not responded to or cannot tolerate the recommended salvage treatment according to guidelines, and have persistent or recurrent disease in any of the following: peripheral blood, bone marrow, lymph nodes, spleen, skin lesions, or other sites.

• Expected survival time of more than 12 weeks;

• ECOG score of 0-2 (Appendix 2);

• No severe mental disorders;

• Basic normal function of important organs:
• Blood routine: white blood cells >1.0×109/L, neutrophils >0.5×109/L, lymphocytes >0.5×109/L, platelets >50×109/L;
• Cardiac function: echocardiography indicates a left ventricular ejection fraction ≥50%, and no significant abnormalities on electrocardiogram;
• Renal function: serum creatinine ≤2.0×ULN;
• Liver function: ALT and AST ≤3.0×ULN (for patients with liver invasion

• 5.0×ULN);
• Total bilirubin ≤2.0×ULN (for patients with Gilbert's syndrome ≤3.0×ULN);
• Blood oxygen saturation >92%. 8. The patient or their legal guardian agrees to participate in this clinical trial and signs the ICF, indicating their understanding of the purpose and procedures of the clinical trial and willingness to participate in the study.

Exclusion criteria

• Presence of active central nervous system invasion during screening;
• Receipt of anti-tumor therapies prior to screening, including chemotherapy, targeted therapy, or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter), except for those who have confirmed disease progression after treatment;
• Occurrence of cerebrovascular accident or epileptic seizure within 6 months prior to screening;
• Presence of active or uncontrolled infection requiring systemic treatment within 1 week prior to screening;
• Presence of any of the following cardiac diseases:

• Congestive heart failure at New York Heart Association (NYHA) class III or IV;
• Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months prior to enrollment;
• Clinically significant ventricular arrhythmia, or history of unexplained syncope (excluding cases caused by vasovagal or dehydration);
• History of severe non-ischemic cardiomyopathy;
• Combination with active autoimmune diseases requiring long-term immunosuppressive therapy;
• Presence of other malignancies, except for adequately treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, localized prostate cancer after radical surgery, and ductal carcinoma in situ after radical surgery.
• Receipt of live attenuated vaccines within 4 weeks prior to screening;
• Pregnant or breastfeeding women, as well as male or female subjects who plan to have children within 1 year after receiving CAR-NK cell infusion;
• Other conditions that the investigator deems unsuitable for participation in the study.