Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis

PRIMARY OBJECTIVES: I. To confirm the safety and tolerability of daratumumab, ixazomib, and dexamethasone (DId) in patients with amyloid light chain (AL) amyloidosis. II. To determine the recommended phase 2 dose (RP2D) of daratumumab, ixazomib, and dexamethasone in subjects with AL amyloidosis. SECONDARY OBJECTIVES: I. To determine the hematologic response rate of daratumumab, ixazomib, and dexamethasone in patients with AL amyloidosis. II. To determine cardiac and renal organ response rate of daratumumab, ixazomib, and dexamethasone in patients with AL amyloidosis. III. To determine time to next therapy. IV. To determine the time to response. V. To determine the duration of response. VI. To determine progression free survival (PFS). VII. To determine overall survival (OS). OUTLINE: This is a dose-escalation study of dexamethasone. Participants receive daratumumab intravenously (IV) over 3.5-6.5 hours on days 1, 8, 15, and 22 of courses 1-2, on days 1 and 15 of courses 3-6, and on day 1 of courses 7-12. Participants also receive ixazomib orally (PO) on days 1, 8, and 15, and dexamethasone IV over 15 minutes or PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unaccepted toxicity. After completion of study treatment, participants are followed up at 30 days and then every 90 days for 24 months.