eligibility_summary
Adults ≥18 with systemic AL amyloidosis (non-BM tissue by IHC/Congo red or EM), t(11,14) by UCSF FISH, ≥1 prior therapy (no steroid-only), limited prior CD38 if responsive, measurable LC disease, organ involvement, ECOG ≤2, adequate labs/CrCl ≥30, washouts, contraception, and flu/pneumo vaccines. Exclude: CD38 progression, prior BCL-2, non-AL or MM, severe cardiac, planned SCT, recent cancer, severe COPD/asthma, active HIV/HBV/HCV, strong CYP3A drugs/foods, recent major surgery, pregnancy/live vaccines.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial status: Withdrawn. Design: Phase 1/2 study in previously treated systemic AL amyloidosis with t(11,14). Interventions and mechanisms: • Venetoclax (Venclexta) – oral small‑molecule BH3‑mimetic BCL‑2 inhibitor, induces apoptosis of BCL‑2–dependent plasma cells (t(11,14) often BCL‑2–high). • Daratumumab SC (Darzalex) – anti‑CD38 IgGκ monoclonal antibody, targets CD38 on clonal plasma cells, mediating ADCC, CDC, ADCP, and direct apoptosis. • Dexamethasone – glucocorticoid corticosteroid, lympholytic and anti‑inflammatory, enhances antitumor activity. Targets: Pathogenic CD38+ clonal plasma cells producing amyloidogenic light chains, BCL‑2 survival pathway, CD38 surface antigen. Companion test: CCND1‑IGH FISH to confirm t(11,14). Goal: eradicate the plasma cell clone, reduce free light chains, and improve organ outcomes.