eligibility_summary
Eligible: adults 18–75 with newly diagnosed, biopsy‑proven AL amyloidosis with major organ (heart/kidney/liver) involvement, A/B: Mayo 2004 I–IIIA, C: IIIB (NT‑proBNP >8500 ng/L plus cTnT >0.035 μg/L or cTnI >0.01 g/L), consent, survival ≥12 weeks, ECOG ≤2, women of childbearing potential use effective contraception from consent to 365 days post‑infusion. Exclude: eGFR <30 mL/min/1.73 m2, multiple myeloma, infection needing treatment ≤30 days, pregnant/breastfeeding, severe allergy to monoclonal antibodies/immune modulators, other unsuitability.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06376214 tests daratumumab-based therapy in newly diagnosed systemic AL amyloidosis: (A) long-term daratumumab+dexamethasone, (B) the same for 2 cycles then ASCT, and (C) DPD: daratumumab+dexamethasone+pomalidomide for stage IIIb. Mechanisms/types: Daratumumab is an anti-CD38 IgGκ monoclonal antibody that targets CD38 on clonal plasma cells, inducing CDC, ADCC/ADCP, apoptosis, and depleting CD38+ immunosuppressive cells, it can inhibit CD38 ectoenzyme (NADase) activity. Dexamethasone is a glucocorticoid (GR agonist) promoting lymphoid/plasma-cell apoptosis and dampening cytokines. Pomalidomide is an IMiD that binds cereblon, degrades IKZF1/3, suppresses plasma cells, and boosts T/NK activity, anti-angiogenic. ASCT uses high-dose melphalan (alkylator) to ablate the plasma-cell clone with stem-cell rescue. Targets/pathways: CD38+ plasma cells (light-chain production), complement/Fc effector killing, cereblon–IKZF axis, glucocorticoid signaling, NK/macrophage effectors, DNA crosslinking (melphalan).