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

A Clinical Study to Evaluate the Safety and Efficacy of ICG415 CAR-T Cells in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia

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.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with limited treatment options for patients who are relapsed or refractory (R/R) to standard therapies. Leukemic blasts in R/R AML frequently co-express CD33 and CLL1, while sparing normal hematopoietic stem cells, making them rational targets for chimeric antigen receptor (CAR) T-cell therapy.

This phase I, single-arm, open-label study evaluates ICG415 CAR-T Cells in patients with R/R AML. After leukapheresis and ex vivo modification, patients receive a single CAR-T cell infusion following lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Primary objectives are safety and tolerability, including dose-limiting toxicities (DLTs), cytokine release syndrome (CRS), and neurological events. Secondary objectives include response rate (CR/CRi/PR), minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS).

All participants will be followed for up to 24 months with regular clinical, laboratory, and imaging evaluations to monitor both treatment efficacy and potential complications.

Inclusion Criteria:

1. Written informed consent approved by IRB/IEC obtained from subject or legally authorized representative prior to any screening procedures.
2. Age ≥ 18 years and ≤ 70 years at the time of informed consent signing.
3. 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.
4. Bone marrow leukemic blasts positive for both CLL-1 and CD33 by flow cytometry.
5. If circulating blasts are detectable at screening, tumor cell surface immunophenotype must be CD4 and CD8 double-negative by flow cytometry.
6. ECOG performance status 0-2.
7. Expected overall survival > 3 months.
8. 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.

Exclusion Criteria:

1. Prior receipt of CAR-T cell therapy or other genetically modified cell therapy prior to informed consent.
2. 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.
3. Active uncontrolled infection: positive HBsAg/HBV-DNA, active HCV-RNA positivity, HIV positive, positive syphilis antibody, active uncontrolled EBV or CMV viremia.
4. Unstable severe systemic disease requiring continuous medication.
5. Grade >2 bleeding within 30 days before screening or chronic long-term anticoagulant treatment.
6. Uncontrolled life-threatening bacterial, fungal or viral infection.
7. Non-leukemic central nervous system organic disease or active CNS-2/CNS-3 leukemia; previously treated and resolved CNS leukemia is permitted.
8. Concurrent other malignant tumor except cured in-situ carcinoma or malignancies with ≥5 years continuous complete remission.
9. Live-attenuated vaccines within 30 days before screening or planned within 3 months after CAR-T infusion.
10. Received any other investigational medicinal product within 3 months prior to ICF signature.
11. Allogeneic hematopoietic stem cell transplantation within 6 months before screening.
12. Pregnant or breastfeeding women.
13. Suicidal tendency, ongoing alcohol or illicit drug dependence.
14. Known hypersensitivity to investigational product, excipients or concomitant drugs.
15. Any other condition judged inappropriate for trial entry by investigator.