NCT06428019: Prospective open-label Phase IIb/III trial in previously untreated CLL/SLL optimizing venetoclax ramp-up and assessing tumor lysis syndrome risk when combined with obinutuzumab or acalabrutinib (four arms: 5-week or modified ramp-ups). Drugs and mechanisms: Venetoclax (oral small-molecule BH3-mimetic BCL-2 inhibitor) triggers apoptosis of CLL B cells, Obinutuzumab (IV humanized type II anti-CD20 monoclonal antibody) depletes B cells via enhanced ADCC/ADCP and direct cell death, Acalabrutinib (oral covalent Bruton tyrosine kinase [BTK] inhibitor) blocks B-cell receptor signaling, reducing proliferation and survival. Cells/pathways targeted: malignant CD20+ B lymphocytes, anti-apoptotic BCL-2 pathway, BTK/BCR→NF-κB survival signaling, engagement of innate effector cells (NK cells/macrophages) for ADCC/ADCP. Primary focus: safety/TLS risk during combination therapy and ramp-up optimization.