eligibility_summary
Eligibility: AML (WHO 2016) with CD33/CD123+ blasts, age ≥12, relapsed/refractory after ≥1 prior regimen, ECOG 0–2, adequate cardiac/renal/hepatic function, WBC <20k (hydroxyurea allowed), consent/adherence, WOCBP: negative test+contraception. Exclude: prior tagraxofusp, primary resistance/progression on gemtuzumab, active CNS AML, HSCT <60d or active GVHD or immunosuppression, recent chemo (<14d), persistent ≥G2 tox, major CV/pulmonary disease, uncontrolled illness/infection, pregnancy, HIV/HBV/HCV, confounding malignancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase Ia/Ib trial in relapsed/refractory AML testing two targeted cytotoxic biologics: 1) Tagraxofusp-erzs: a recombinant cytokine–toxin fusion (IL-3 linked to truncated diphtheria toxin). Mechanism: binds IL-3 receptor alpha (CD123) on AML cells, is internalized, and the toxin inhibits protein synthesis via EF-2 ADP-ribosylation, killing CD123+ blasts/progenitors. Drug type: targeted toxin/immunotoxin. 2) Gemtuzumab ozogamicin: an anti-CD33 antibody–drug conjugate carrying calicheamicin. Mechanism: binds CD33 on AML blasts, internalizes, and releases calicheamicin to cause DNA double-strand breaks and apoptosis. Drug type: ADC. Targets/pathways: dual targeting of CD123 and CD33 on AML blasts and leukemic stem/progenitor cells, IL-3R/translation machinery and DNA damage–apoptosis pathways. Goal: define RP2D and assess safety.