Not Yet RecruitingPhase 1

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

18 participantsStarted 2026-06-01

Plain-language summary

Relapsed/refractory acute myeloid leukemia (R/R AML) currently lacks effective CAR-T therapeutic agents due to the absence of tumor-specific target antigens. Most AML-associated antigens are expressed on normal hematopoietic stem/progenitor cells (HSPCs) and healthy tissues, increasing the risk of on-target off-tumor toxicity and non-neoplastic toxicity. CD33 is present on leukemic cells in over 80% of AML patients. Compared with CLL-1, CD123 and other targets, CD33 exhibits higher expression across diverse AML subtypes, reducing the risk of treatment failure and relapse caused by antigen escape and thus serving as an ideal therapeutic target for AML. However, conventional CD33-targeted CAR-T cells demonstrate suboptimal efficacy in clinical trials, accompanied by significant toxicity and inadequate in vivo expansion. To further investigate the safety and efficacy of CAR-T therapy for AML, our center has initiated a clinical trial of functionally optimized CD33 CAR-T (FO33 CAR-T) cells for R/R AML. We constructed a lentiviral CAR vector containing the CD33-targeting scFv, 4-1BB, and CD3ζ, followed by insertion of adjuvant molecule X. FO33 CAR-T cells showed superior cytotoxicity against AML cell lines and enhanced biological activity compared with conventional CD33 CAR-T cells, and exerted safe and effective antitumor effects in preclinical models. This single-center, open-label, prospective clinical trial aims to evaluate the safety and efficacy of FO33 CAR-T cells in patients with R/R AML, as well as to characterize the pharmacokinetic and pharmacodynamic (PK/PD) profiles of this therapy.

Who can participate

Age range14 Years – 75 Years

SexALL

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Inclusion 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.
✓. Creatinine ≤1.5×ULN;
✓. Left ventricular ejection fraction ≥50%;
✓. Blood oxygen saturation\>90%;
✓. Total bilirubin ≤1.5×ULN; ALT and AST ≤2.5×ULN.

Exclusion criteria

✕. Atrial fibrillation;
✕. Myocardial infarction (MI) within the past 12 months;
✕. Prolonged QT syndrome or secondary QT prolongation as determined by the investigator;

What they're measuring

Evaluate the Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia

Timeframe: up to one month after the CAR-T infusion

Evaluate the Complete Response rate of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia

Timeframe: one month and three month after the CAR-T infusion

Trial details

NCT IDNCT07538713

SponsorQi deng

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2028-05-31

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