eligibility_summary
Inclusion: Age >28 d–<22 y, AML (WHO) or de novo AML genetics (<20% blasts), myeloid sarcoma, primary MDS ≥10% blasts, or WBC blasts ≥1,000/μL, only 1 IT dose + hydroxyurea or low‑dose cytarabine (≤200 mg/m^2/d ≤7 d), negative pregnancy test, contraception during +6 mo, consent, bilirubin ≤1.5×ULN. Exclusion: therapy‑related AML, Down syndrome, APL, CML‑BC, JMML, Fanconi/Kostmann/Shwachman/other BMF, uncontrolled infection/major illness, prior anthracycline/anthracenedione, CYP3A inducers/inhibitors ≤3 d.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
manual_review_required
ai_summary
Phase 2 pediatric AML trial testing venetoclax plus conventional chemotherapy. Interventions and mechanisms: • Venetoclax (oral small-molecule BH3 mimetic, selective BCL‑2 inhibitor) to prime apoptosis in AML blasts. • Cytarabine (pyrimidine antimetabolite, incorporated into DNA, inhibits polymerase). • Daunorubicin/Idarubicin (anthracyclines, DNA intercalation, topoisomerase II inhibition, ROS). • Etoposide (topoisomerase II inhibitor). • Mitoxantrone (anthracenedione, intercalation/topo II inhibition). • Fludarabine (purine analog, inhibits DNA polymerase and ribonucleotide reductase, augments ara‑CTP). • Azacitidine (hypomethylating DNMT inhibitor). • Gemtuzumab ozogamicin (anti‑CD33 ADC delivering calicheamicin causing DNA DSBs). • Gilteritinib (FLT3 tyrosine kinase inhibitor for FLT3‑activated disease). Targets: CD33+ AML myeloblasts/leukemic progenitors, BCL‑2–dependent survival pathway, FLT3‑mutant signaling, DNA replication and topoisomerase II, and aberrant DNA methylation.