This trial is active, not recruiting.

Conditions cancer, hematologic malignancies, multiple myeloma, oncology, bone metastases, multiple myeloma bone lesions
Treatments denosumab, zoledronic acid
Phase phase 3
Target RANKL
Sponsor Amgen
Collaborator Daiichi Sankyo Inc.
Start date May 2012
End date July 2016
Trial size 1718 participants
Trial identifier NCT01345019, 20090482


The purpose of this study is to determine if denosumab is non-inferior to zoledronic acid in the treatment of bone disease from multiple myeloma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose supportive care
(Active Comparator)
Zoledronic acid 4 mg (adjusted for renal function) IV over at least 15 minutes + Placebo SC Q4W (n = 760)
zoledronic acid
Zoledronic acid 4 mg (adjusted for renal function) IV over at least 15 minutes Q4W (n = 760)
Denosumab 120 mg SC + Placebo IV over at least 15 minutes Q4W (n = 760)
Denosumab 120 mg SC

Primary Outcomes

Time to the first on-study skeletal related event (SRE) (non-inferiority test)
time frame: Approximately 50 months

Secondary Outcomes

Time to the first-and-subsequent SRE (superiority test, using multiple event analysis)
time frame: Approximately 50 months
Time to the first on-study SRE (superiority test)
time frame: Approximately 50 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Documented evidence of multiple myeloma (per local assessment; see section 7.2): - 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; see section 7.2): 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

Additional Information

Official title A Randomized, Double-Blind, Multicenter Study of Denosumab Compared With Zoledronic Acid in the Treatment of Bone Disease in Subjects With Newly Diagnosed Multiple Myeloma
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Amgen.
Location data was received from the National Cancer Institute and was last updated in August 2016.