This single-arm, open-label phase I trial evaluates the safety and tolerability of ICG415, autologous CAR-T cells targeting CD33 and CLL1, in patients with relapsed or refractory acute myeloid leukemia (AML). Subjects receive lymphodepleting chemotherapy followed by autologous CAR-T infusion. The primary goal is to assess safety and preliminary anti-leukemic efficacy in patients failing standard AML therapies.
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.
Prior receipt of CAR-T cell therapy or other genetically modified cell therapy prior to informed consent.
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.
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.
Sequential
Anti-CD33-CLL1 CAR-T cells (ICG415) following lymphodepleting fludarabine and cyclophosphamide
Biological/VaccineAnti-CD33, Anti-CLL1 Compound CAR-T Cells
Incidence of Dose-Limiting Toxicities (DLTs)
DLTs assessed according to the protocol-defined criteria.
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
Frequency and severity of TEAEs graded by NCI-CTCAE Version 5.0, including changes from baseline in vital signs, physical examination, 12-lead ECG, and clinical laboratory parameters (complete blood count, urinalysis, blood chemistry, coagulation function, etc.).
Objective Response Rate (ORR) at Months 1, 3, and 6
ORR defined as proportion of subjects achieving complete remission (CR), complete remission with incomplete count recovery (CRi), or complete remission with partial hematological recovery (CRh) per response criteria.
Rates of CR, CRi, and PR at Year 1 and Year 2
Proportion of subjects achieving complete remission (CR), complete remission with incomplete count recovery (CRi), and partial remission (PR) at 1 and 2 years post infusion.
Cumulative Incidence of Relapse (CIR) at Year 1 and Year 2
Cumulative incidence of disease relapse at 1 and 2 years after CAR-T cell infusion.
Duration of Response (DOR)
Time from first objective response (CR, CRi, or CRh) to relapse or death, whichever occurs first.
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