Anti-CD33-CLL1 CAR-T Cells (ICG415) for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Prior treatment

• Prior receipt of CAR-T cell therapy or other genetically modified cell therapy prior to informed consent.
• Grade \>2 bleeding within 30 days before screening or chronic long-term anticoagulant treatment.
• Non-leukemic central nervous system organic disease or active CNS-2/CNS-3 leukemia; previously treated and resolved CNS leukemia is permitted.
• Concurrent other malignant tumor except cured in-situ carcinoma or malignancies with ≥5 years continuous complete remission.
• Live-attenuated vaccines within 30 days before screening or planned within 3 months after CAR-T infusion.
• Received any other investigational medicinal product within 3 months prior to ICF signature.
• Allogeneic hematopoietic stem cell transplantation within 6 months before screening.
• Suicidal tendency, ongoing alcohol or illicit drug dependence.
• Known hypersensitivity to investigational product, excipients or concomitant drugs.

Other illness

• Active uncontrolled infection: positive HBsAg/HBV-DNA, active HCV-RNA positivity, HIV positive, positive syphilis antibody, active uncontrolled EBV or CMV viremia.
• Unstable severe systemic disease requiring continuous medication.
• Uncontrolled life-threatening bacterial, fungal or viral infection.
• Any other condition judged inappropriate for trial entry by investigator.

Lab values

• Severe major organ dysfunction: Renal: eGFR \< 50 mL/min (Cockcroft-Gault); Hepatic: ALT/AST \> 3 × ULN (\>5×ULN if disease-related), total bilirubin \> 2 × ULN (\>3×ULN for Gilbert syndrome); Cardiac: LVEF \< 50%, room air SpO₂ \<94%, uncontrolled severe cardiac disease.

Other

• Pregnant or breastfeeding women.

• Written informed consent approved by IRB/IEC obtained from subject or legally authorized representative prior to any screening procedures.
• Age ≥ 18 years and ≤ 70 years at the time of informed consent signing.
• Diagnosis of acute myeloid leukemia (AML) per 2022 WHO Classification, meeting criteria for relapsed/refractory (R/R) AML as defined in the Chinese Guidelines for the Diagnosis and Management of Relapsed/Refractory Acute Myeloid Leukemia (2023 Edition): Relapsed AML: Reappearance of leukemic blasts in peripheral blood, bone marrow blasts ≥5%, or extramedullary leukemic infiltration after complete remission (CR). Refractory AML: failure to achieve CR after two cycles of standard induction chemotherapy; early relapse within 12 months post-CR; late relapse with salvage chemotherapy resistance; ≥2 disease relapses or persistent extramedullary disease.
• Bone marrow leukemic blasts positive for both CLL-1 and CD33 by flow cytometry.
• If circulating blasts are detectable at screening, tumor cell surface immunophenotype must be CD4 and CD8 double-negative by flow cytometry.
• ECOG performance status 0-2.
• Expected overall survival \> 3 months.
• Females of childbearing potential: negative serum pregnancy test and effective contraception for 1 year post-infusion. Males of reproductive potential: effective barrier contraception for 1 year post-infusion and no sperm donation within 1 year after infusion.