eligibility_summary
Eligibility: 1-<18 yrs with first-relapse HR CD22+ BCP-ALL, BM blasts >=5%, relapse 18-30 mo from dx or <=6 mo post-therapy, no VHR genetics (eg KMT2A::AFF1, TCF3-HLF/PBX1, hypodiploidy, TP53). eGFR/eCrCl >=30, AST/ALT <=5xULN, bilirubin <=1.5xULN, SF >=30% or EF >50%. Prior thrombosis allowed with prophylaxis. BM+testicular relapse allowed with orchiectomy. Exclude: hepatic SOS/liver failure, prior allo-HSCT/CAR-T, isolated EM disease, Ph+ ALL, prior calicheamicin Ab (eg InO/gemtuzumab), active infection, allergy to PEG- and Erwinia-ASP.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 2 randomized, open-label induction study in pediatric high-risk first-relapse CD22+ B-cell precursor ALL comparing: • Inotuzumab ozogamicin (InO): an antibody–drug conjugate (humanized anti‑CD22 IgG4 linked to calicheamicin). Mechanism: binds CD22 on B‑cell precursor lymphoblasts, internalizes, releases calicheamicin to cause DNA double‑strand breaks and apoptosis. • ALLR3 chemotherapy: – Mitoxantrone (anthracenedione): topoisomerase II inhibitor → DNA strand breaks. – Vincristine (vinca alkaloid): inhibits tubulin polymerization → mitotic arrest. – Dexamethasone (glucocorticoid): activates GR to induce lymphoid apoptosis and anti‑proliferative effects. – PEG‑asparaginase or Erwinia‑asparaginase (enzymes): deplete asparagine → impaired protein synthesis in leukemic blasts. Targets/pathways: CD22+ B‑cell precursors, DNA damage (calicheamicin, topo II), microtubules, glucocorticoid receptor signaling, and asparagine metabolism/protein synthesis.