eligibility_summary
Adults 18–65 with untreated CLL per iwCLL 2018 and active disease, high‑risk (unmutated IGHV and/or TP53 mutation/del17p), ECOG 0–1, CIRS<6, CrCl>30, adequate counts/liver, QTcF≤450, negative pregnancy test, contraception, consent. Exclude Richter’s/CNS disease, active/recent cancer, major cardiac/bleeding/autoimmune illness, serious infection (HBV/HCV/HIV/TB), renal/liver failure, interacting drugs, recent surgery/live vaccines, pregnancy/breastfeeding, malabsorption, other trials.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial NCT05478512 tests an MRD-tailored, front-line regimen in high-risk CLL: induction with venetoclax + obinutuzumab, then continuation based on MRD (venetoclax alone if uMRD, venetoclax + zanubrutinib if residual disease, possible zanubrutinib monotherapy thereafter). Drugs and mechanisms: • Venetoclax (oral small-molecule BH3 mimetic) inhibits BCL-2 to trigger apoptosis of CLL B cells. • Obinutuzumab (IV, type II glycoengineered anti-CD20 monoclonal antibody) binds CD20 on B cells, inducing direct cell death and enhanced Fc-mediated ADCC/ADCP. • Zanubrutinib (oral covalent Bruton’s tyrosine kinase [BTK] inhibitor) suppresses B-cell receptor signaling (e.g., NF-κB, PLCγ2), reducing B-cell survival/proliferation and trafficking. Targets: malignant CD20+ B cells, BCL-2 antiapoptotic pathway, BTK/BCR signaling, immune effector mechanisms via ADCC/ADCP.