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.