Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Patients With Multiple Myeloma

Inclusion Criteria:

Documented evidence of multiple myeloma (per local assessment):
Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma, and
Monoclonal protein present in the serum and/or urine
Radiographic (X-ray, or computer tomography [CT]) evidence of at least 1 lytic bone lesion (or at least 1 focal lesion per magnetic resonance imaging [MRI])
Plan to receive or is receiving primary frontline anti-myeloma therapies
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Age ≥ 18 years

Adequate organ function, as defined by the following criteria (per central or local laboratory values):

Serum aspartate aminotransferase (AST) ≤ 2.0 x upper limit of normal (ULN)
Serum alanine aminotransferase ≤ (ALT) 2.0 x ULN
Serum total bilirubin ≤ 2.0 x ULN
Creatinine clearance ≥ 30 mL/min
Serum calcium or albumin-adjusted serum calcium 2.0 mmol/L (8.0 mg/dL) and 2.9 mmol/L (11.5 mg/dL)
Written informed consent before any study-specific procedure is performed

Exclusion Criteria:

Nonsecretory multiple myeloma based upon standard M-component criteria (ie, measurable serum/urine M-component) unless the baseline serum free light chain level is elevated
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Plasma cell leukemia
More than 30 days of previous treatment (before screening) with anti-myeloma therapy (does not include radiotherapy or a single short course of steroid [ie, less than or equal to the equivalent of dexamethasone 60 mg/day for 4 days]).
Planned radiation therapy or surgery to the bone (does not include procedures performed before randomization)
Prior administration of denosumab
Use of oral bisphosphonates with a cumulative exposure of more than 1 year
More than 1 previous dose of IV bisphosphonate administration
Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
Active dental or jaw condition which requires oral surgery, including tooth extraction
Non-healed dental/oral surgery, including tooth extraction
Planned invasive dental procedures

Evidence of any of the following conditions per subject self-report or medical chart review:

Any prior invasive malignancy within 5 years before randomization
Any non-invasive malignancy not treated with curative intent or with knownactive disease within 5 years before randomization
Major surgery or significant traumatic injury occurring within 4 weeks before randomization
Active infection with Hepatitis B virus or Hepatitis C virus
Known infection with human immunodeficiency virus (HIV)
Active infection requiring IV anti-infective therapy
Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after end of treatment
Female subject of child bearing potential is not willing to use highly effective contraception during treatment and for 5 months after the end of treatment (see section 6.3)
Known sensitivity to any of the products to be administered during the study (eg, mammalian derived products, calcium or vitamin D)
Subject is receiving or is less than 30 days since ending other experimental device or drug (no marketing authorization for any indication)
Subject will not be available for follow-up assessment
Any major medical or psychiatric disorder that in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results