Study Testing Radium-223 Dichloride in Relapsed Multiple Myeloma

Inclusion Criteria:

* Subject must have documented monoclonal plasma cells in the bone marrow of ≥10%, as defined by their institutional standard at some point in their disease history or the presence of a biopsy proven plasmacytoma.
* Subjects must have received at least 1 and not more than 3 previous lines of treatment and have had a response to at least 1 prior Treatment in the past (i.e., achieved a minimal response \[MR\] or better) according to the IMWG uniform response criteria.
* Subject must be non-refractory to bortezomib (Refractory is defined: progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy).
* Subjects must have documented evidence of progressive disease according to the IMWG uniform response criteria following the last multiple myeloma treatment.
* Subjects must have measurable disease defined as at least 1 of the following:

  * Serum M-protein defined by the following:

    * IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL (measured by protein electrophoresis \[PEP\]);
    * IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level ≥0.5 g/dL (measured by PEP).
  * Urine M-protein ≥200 mg/24 hours (any immunoglobulin heavy chain type measured by PEP).
  * Serum free light chain (FLC) ≥10 mg/dL with abnormal ratio in subjects with unmeasurable disease by serum or urine PEP.
* ≥1 bone lesion identifiable by radiograph, computed tomography (CT), positron emission tomography - computed tomography (PET-CT), or magnetic resonance imaging (MRI).
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
* Adequate hepatic function, with total bilirubin ≤1.5 x upper limit of normal (ULN) (except for Gilbert Syndrome: total bilirubin \< 3.0 x ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN.
* Absolute neutrophil count (ANC) ≥1.5 × 10e9/L, hemoglobin (Hb) ≥9.0 g/dL, and platelet count ≥75.0 × 10e9/L independent of transfusion of red blood cells (RBC) or platelet concentrates and independent of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF).
* International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) ≤ 1.5 x ULN. Prothrombin time (PT) may be used instead of INR if ≤ 1.5 x ULN.

Exclusion Criteria:

* Systemic glucocorticoid therapy (prednisone \>10 mg/day orally or equivalent) within the last 4 weeks prior to first dose, unless tapered and on a stable dose (prednisone ≤10 mg/day orally or equivalent) for at least 1 week.
* Subjects with known POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light-chain (AL) amyloidosis.
* Plasma cell leukemia (defined by plasma cell \>20%, and/or an absolute plasma cell count of \>2 x 10e9/L in peripheral blood).
* Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic (PK) half-lives (t1/2) of the treatment, whichever is longer, before the date of start of treatment.
* Radiation therapy in the previous 4 weeks prior to first dose.
* Prior treatment with radium-223 dichloride or any experimental radiopharmaceutical.
* Congestive heart failure (New York Heart Association \[NYHA\] class III to IV), symptomatic cardiac ischemia, unstable angina or myocardial infarction in the previous 6 months prior to first dose, or with a known left ventricular ejection fraction (LVEF) \<40%, cardiomyopathy, pericardial disease, clinically relevant cardiac arrhythmia (CTCAE version 4.03 Grade 2 or higher), clinically significant ECG abnormalities, or screening 12-lead ECG showing a baseline prolonged QT interval (baseline QT interval as corrected by Fridericia's formula \> 470 msec).
* Neuropathy ≥ Grade 2.