A Study of Daratumumab Monotherapy in Previously Untreated Patients With Stage 3B Light Chain (AL) Amyloidosis

Conditions

Daratumumab — DRUG
As of Protocol Amendment 1, all new subjects are dosed with daratumumab subcutaneous injection (SC) co-formulated with recombinant human hyaluronidase rHuPH20. Subjects who already began treatment with daratumumab intravenous (IV) infusion (i.e., prior to Am 1) switch to SC on the next administration date according to the protocol schedule. Subjects receive daratumumab IV at a dose of 16 mg/kg and daratumumab SC at a fixed dose of 1800 mg for the first 8 weeks (Cycles 1 and 2) of treatment and then every 2 weeks for 4 cycles (Cycles 3 to 6) and then every 4 weeks until progression of disease (according to MOD-PFS), unacceptable toxicity or subsequent therapy, for a maximum of 2 years in total. All treatment cycles are 4 weeks (28 days) in length.
Bortezomib Injection — DRUG
Subjects who do not achieve either a hematologic VGPR or better, OR a hematologic PR with a major organ response by Cycle 4 Day 1 may receive at Investigator's discretion, in addition to daratumumab, bortezomib at a dose of 1.3 mg/m2 weekly for a maximum of 6 cycles as a subcutaneous injection
Dexamethasone oral tablet — DRUG
Subjects who do not achieve either a hematologic VGPR or better, OR a hematologic PR with a major organ response by Cycle 4 Day 1 may receive at Investigator's discretion, in addition to daratumumab low dose dexamethasone at a maximum total dose of 20 mg weekly.

This is an open-label, multicenter, Phase 2 study in subjects with newly diagnosed stage 3B light chain (AL) amyloidosis.

Experimental: Daratumumab
Daratumumab monotherapy 16 mg/kg intravenous infusion (iv) or 1800 mg subcutaneous injection (sc) weekly for Cycles 1-2, every 2 weeks for Cycles 3-6 and every 4 weeks thereafter. Subjects who do not achieve either a hematologic VGPR or better, OR a hematologic PR with a major organ response by Cycle 4 Day 1 may receive, in addition to daratumumab, bortezomib (for a maximum of 6 cycles) and low dose dexamethasone.

overall survival [ Time Frame: 6 months ]