Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet

Prior treatment

• Previous diagnosis of amyloidosis associated with myeloma
• Toxicity requiring discontinuation of lenalidomide therapy
• Prior treatment with pomalidomide

Other illness

• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Myelodysplastic syndrome

Lab values

• Plasma cell leukemia ( greater than 2.0 × 109/L circulating plasma cells by differential). If automated differential shows ≥ 20% of other cells, obtain manual differential to identify other cells.

Other

• Primary refractory multiple myeloma
• Waldenström macroglobulinemia
• Multiple myeloma of IgM subtype
• Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)

• Subject has provided informed consent prior to initiation of any study specific activities or procedures.
• Male or female subjects age ≥ 18 years
• First or second relapse of multiple myeloma by IMWG criteria (subjects refractory to the most recent line of therapy, excluding carfilzomib, are eligible)
• Refractory to lenalidamide
• Measurable disease with at least 1 of the following assessed within 28 days prior to enrollment:
  • IgG multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
  • IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL
  • urine M-protein ≥ 200 mg per 24 hours
  • in subjects without measurable serum or urine M-protein, serum-free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
• Must have at least a PR to at least 1 line of prior therapy
• Prior therapy with proteasome inhibitors is allowed. Subjects receiving prior carfilzomib therapy must have achieved at least a PR, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval from their last dose of carfilzomib
• ECOG PS of 0 to 2