CLL-1/CD70 Dual-Target CAR-T Cell Therapy for Acute Myeloid Leukemia

Prior treatment

• Concurrent progressive malignancy other than acute myeloid leukemia.

Other illness

• A history of severe pulmonary disease with impaired lung function.
• Severe active infection that cannot be effectively controlled.
• Severe autoimmune disease or congenital immunodeficiency.
• Active hepatitis, defined as hepatitis B virus DNA (HBV-DNA) or hepatitis C virus RNA (HCV-RNA) levels above the lower limit of detection.
• Human immunodeficiency virus (HIV) infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection.
• A history of severe allergic reactions to biological products, including antibiotics.
• Severe infection is defined as sepsis or an infection with an uncontrolled infectious focus. Participants may be enrolled after the infection has been adequately controlled.

Lab values

• Severe cardiac dysfunction, or left ventricular ejection fraction (LVEF) \<50%.
• Any other severe physical or psychiatric disorder or clinically significant laboratory abnormality that may increase the risk associated with study participation, interfere with the interpretation of study results, or, in the investigator's judgment, make the participant unsuitable for participation in the study.
  • Note:

• Voluntarily agrees to participate in the study, has signed the informed consent form, and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
• Diagnosis of acute myeloid leukemia (AML), excluding acute promyelocytic leukemia (APL), according to the 2022 World Health Organization (WHO) classification; target testing shows CLL-1 expression \>=50% and/or CD70 expression \>=50%.
• Diagnosis of AML meeting at least one of the following:
  • Relapsed AML: reappearance of leukemic cells in the peripheral blood after achieving complete remission (CR), bone marrow blasts \>=5% (excluding bone marrow regeneration after consolidation chemotherapy or other non-leukemic causes), or the presence of extramedullary leukemic infiltration.
  • Refractory AML: newly diagnosed AML with no response after one course of standard induction therapy; relapse within 12 months after achieving CR followed by consolidation/intensification therapy; relapse more than 12 months after CR with failure to respond to conventional chemotherapy; two or more relapses; or persistent extramedullary leukemia.
• Male or female participants aged 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Estimated life expectancy of more than 3 months from the date of signing the informed consent form.
• Hemoglobin (HGB) \>=60 g/L (transfusion permitted).
• Adequate renal, hepatic, cardiac, and pulmonary function, defined as follows:
  • Serum creatinine \<=1.5 x the upper limit of normal (ULN);
  • Left ventricular ejection fraction (LVEF) \>=50%;
  • Oxygen saturation \>90% on room air;
  • Total bilirubin \<=1.5 x ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<=2.5 x ULN;
  • No clinically significant pleural effusion, and oxygen saturation \>92% on room air at baseline.
• Participants with reproductive plans must agree to use contraception before enrollment and for 6 months during/after the study. Participants must immediately notify the investigator if pregnancy occurs or is suspected.