eligibility_summary
Adults (≥18) with newly diagnosed untreated AML (≥20% blasts), CD123+ by central flow, prior MDS/CMML/MDS/MPN treated with ≥2 HMA cycles, WBC <30 (after cytoreduction allowed), ECOG 0–2, adequate organs, LVEF ≥45, contraception, controlled HIV/HBV/HCV allowed. Exclude: candidates for intensive chemo, APL, CNS AML, prior tagraxofusp, recent therapy (<14d) or allo-SCT (<60d), active GVHD/immunosuppression, other active cancers, major CV/pulmonary disease, uncontrolled infection, pregnancy, or other high-risk conditions.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II single-arm study in newly diagnosed secondary AML after prior HMA exposure, restricted to CD123-positive disease. Interventions: 1) Tagraxofusp (immunotoxin, recombinant fusion of IL‑3 to truncated diphtheria toxin). Mechanism: binds CD123 (IL‑3Rα), is internalized, ADP‑ribosylates EF‑2, blocks protein synthesis, inducing apoptosis. 2) Azacitidine (hypomethylating cytidine analog). Mechanism: inhibits DNA methyltransferases, causing DNA hypomethylation and direct cytotoxicity to malignant hematopoietic cells. 3) Venetoclax may be used per protocol (small‑molecule BCL‑2 inhibitor). Mechanism: blocks anti‑apoptotic BCL‑2, priming AML cells for mitochondrial apoptosis. Targeted cells/pathways: CD123+ AML blasts and leukemic stem/progenitor cells, IL‑3R–mediated internalization/protein synthesis, epigenetic DNA methylation, intrinsic apoptosis via BCL‑2.