eligibility_summary
Eligibility: ≥18 with AML unlikely curable: refractory/PR or relapse after allo‑HCT (incl. MRD), if post‑transplant, off systemic immunosuppression ≥1 mo. Requires suitable donor and adequate organs (CrCl>40, AST/ALT ≤5×ULN [≤20× if disease‑related], bili <2 [≤3 if Gilbert]), LVEF ≥40%, DLCO >45%, ECOG 0–1, consent, contraception. Exclude: pregnancy/lactation, active HBV/HCV/HIV, current steroids/immunosuppressants, uncontrolled illness, CNS disease, allergy to HSA/DMSO/Dextran‑40, NYHA III/IV, optic neuritis/CNS immune disease, unstable/recent arrhythmia.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1, single-arm trial in relapsed/refractory AML testing a two-part biological, gene-modified cellular therapy: (1) CD33KO-HSPC transplant—donor hematopoietic stem/progenitor cells gene-edited to knock out CD33, enabling engraftment of CD33‑negative myelopoiesis, (2) CART33—lentivirally transduced T cells expressing an anti‑CD33 CAR with CD3ζ signaling and 4‑1BB costimulation. Mechanisms: CD33KO-HSPC make donor marrow “invisible” to anti‑CD33 activity, reducing on‑target myelotoxicity, CART33 recognizes CD33 on AML cells and induces T‑cell activation and cytotoxicity via CD3ζ/4‑1BB pathways. Targets: CD33 (Siglec‑3) on AML blasts and normal myeloid cells, signaling pathways include CAR‑mediated T‑cell activation (CD3ζ, 4‑1BB). Intended outcome: eliminate CD33+ leukemia while preserving edited donor hematopoiesis.