Selinexor, Carfilzomib, and Dexamethasone Versus Placebo, Carfilzomib, and Dexamethasone in Multiple Myeloma

Inclusion Criteria:

Symptomatic, histologically confirmed MM, based on IMWG guidelines. Patients must have measurable disease as defined by at least one of the following:

Serum M-protein ≥ 1.0 g/dL by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative IgA; or
Urinary M-protein excretion at least 200 mg/24 hours; or
Serum FLC ≥ 100 mg/L, provided that the serum FLC ratio is abnormal.
If serum protein electrophoresis is felt to be unreliable for routine M- protein measurement, then quantitative Ig levels by nephelometry or turbidometry are acceptable.
Must have received ≥ 2 prior anti-MM therapies including a proteasome inhibitor and an IMiD. The most recent proteasome inhibitor must not have been carfilzomib.

Patients previously treated with carfilzomib are eligible as long as they meet the following criteria:

Not received carfilzomib within 6 months (183 days) of Cycle 1 Day 1 (C1D1), and
Carfilzomib was not part of their most recent therapy for the treatment of MM, and
Did not discontinue carfilzomib treatment because of adverse effects.
MM that is refractory to the most recent treatment regimen. Refractory is defined as ≤ 25% response to therapy, or progression during therapy, or progression on or within 60 days after completion of therapy.

Exclusion Criteria:

Smoldering MM.
Active plasma cell leukemia.
MM that does not express M-protein or serum FLC (i.e., non-secretory MM is excluded; plasmacytomas without M-protein or serum FLC are excluded).
Documented active systemic amyloid light chain amyloidosis.
Active MM involving the central nervous system.
Active polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.
Prior autologous stem cell transplantation < 1 month or allogenic stem cell transplantation < 3 months prior to C1D1.
Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.