Functionally Optimized CD33 CAR-T Cell Therapy Targeting Recurrent/Refractory Acute Myeloid Leukemia

Prior treatment

• Concurrent other progressive malignancies.
• Concurrent severe or persistent infections that cannot be effectively controlled.
• Concurrent severe autoimmune diseases or congenital immunodeficiency.

Other illness

• Active graft-versus-host disease (GVHD).
• History of severe pulmonary dysfunction.
• Active hepatitis (HBV-DNA ≥ 500 IU/ml with abnormal liver function or HCV antibody \[HCV-Ab\] positivity, HCV-RNA exceeding the detection limit of analytical methods with abnormal liver function).
• Human immunodeficiency virus (HIV) infection or syphilis infection.
• History of severe allergic reactions to biological products (including antibiotics).
• Presence of central nervous system disorders such as uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, or cerebellar diseases.

Lab values

• Presence of one of the following cardiac criteria:
  • Atrial fibrillation;
  • Myocardial infarction (MI) within the past 12 months;
  • Prolonged QT syndrome or secondary QT prolongation as determined by the investigator;
  • Echocardiographic left ventricular systolic fraction (LVSF) \<30% or left ventricular ejection fraction (LVEF) \<50%;
  • Clinically significant pericardial effusion; New York Heart Association (NYHA) class III or IV heart failure (confirmed by echocardiography within 12 months after treatment).

Other

• Female patients in pregnancy or lactation, or planning pregnancy within 12 months.
• Situations where investigators consider may increase subject risk or interfere with trial outcomes.

• Subjects diagnosed with refractory/recurrent acute myeloid leukemia (excluding M3) who meet any of the following criteria:
  • Relapse: Recurrence of leukemia cells in peripheral blood or ≥5% blast cells in bone marrow after complete remission (CR) of AML (excluding other causes such as bone marrow regeneration following consolidation chemotherapy), or extramedullary leukemia infiltration.
  • Refractory: First-time cases unresponsive to two cycles of standard therapy; relapse within 12 months after consolidation therapy following CR; relapse after 12 months without response to conventional chemotherapy; two or more relapses; persistent extramedullary leukemia.
• During enrollment screening, bone marrow flow cytometry must demonstrate a CD33+ expression rate of ≥80% in leukemia cells and/or pathological immunohistochemical confirmation of CD33+ extramedullary lesions.
• Estimated survival duration exceeding 3 months as of the date of informed consent signing.
• Participants with Eastern Cooperative Oncology Group (ECOG) physical status scores ranging from 0 to 2.
• Age range of 14 years ≤ ≤ 75 years, inclusive, with no gender restriction.
• Hemoglobin (HGB) level ≥70 g/L with transfusion capability.
• Liver/kidney function and cardiopulmonary function meeting the following criteria:
  • Creatinine ≤1.5×ULN;
  • Left ventricular ejection fraction ≥50%;
  • Blood oxygen saturation\>90%;
  • Total bilirubin ≤1.5×ULN; ALT and AST ≤2.5×ULN.
• Acceptance of autologous CART cells with peripheral blood tumor burden ≤ 30%;
• The subject or guardian understands and signs the informed consent form.