eligibility_summary
Adults ≥18 with biopsy‑proven systemic AL amyloidosis and measurable disease (dFLC ≥2 mg/dL), ECOG 0–2 (3 if neuropathy), SBP ≥90, transplant‑eligible with non‑severe cardiac AL (EF ≥40%, NT‑proBNP <5000/BNP <400, TnT <0.06), adequate counts/chemistries, CrCl ≥30, HBV DNA–negative, HCV cured, HIV controlled, no active infection or concurrent myeloma, agree to HD melphalan/ASCT. Step 2: ≥PR after induction, on ≥1 study drug. Step 3: post‑consolidation, no MOD‑PFS, daratumumab not permanently stopped.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase III trial in newly diagnosed AL amyloidosis tests Dara‑VCD induction followed by either consolidation Dara‑VCD or high‑dose melphalan with autologous stem cell transplant (ASCT), then daratumumab maintenance. Interventions and mechanisms: - Daratumumab (anti‑CD38 IgGκ monoclonal antibody, immunotherapy) depletes CD38+ clonal plasma cells via ADCC/CDC/apoptosis, co-formulated with hyaluronidase‑fihj (recombinant hyaluronidase, enhances subcutaneous absorption). - Bortezomib (proteasome inhibitor) blocks the 26S proteasome, suppresses NF‑κB, induces ER‑stress apoptosis. - Cyclophosphamide (alkylating prodrug) and melphalan (alkylator, ASCT conditioning) create DNA crosslinks, killing proliferating plasma cells. - Dexamethasone (corticosteroid, glucocorticoid receptor agonist) is lympholytic and anti‑inflammatory. Targets/pathways: CD38 on plasma cells, ubiquitin–proteasome system, DNA replication/repair, glucocorticoid signaling, immune effector cytotoxicity. Aim: eliminate the light‑chain–producing plasma‑cell clone to improve cardiac/renal outcomes.