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

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ClinicalTrials.gov Identifier: NCT01345019
Recruitment Status : Active, not recruiting
First Posted : April 29, 2011
Last Update Posted : December 22, 2017
Daiichi Sankyo, Inc.
Information provided by (Responsible Party):

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cancer Hematologic Malignancies Multiple Myeloma Oncology Bone Metastases Multiple Myeloma Bone Lesions Drug: Denosumab Drug: Zoledronic acid Other: Placebo SC Other: Placebo IV Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1718 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
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
Actual Study Start Date : May 17, 2012
Primary Completion Date : July 19, 2016
Estimated Study Completion Date : February 1, 2019

Arm Intervention/treatment
Active Comparator: Zoledronic acid 4 mg IV and Placebo SC
Zoledronic acid 4 mg (adjusted for renal function) IV over at least 15 minutes + Placebo SC Q4W (n = 760)
Drug: Zoledronic acid
Zoledronic acid 4 mg (adjusted for renal function) IV over at least 15 minutes Q4W (n = 760)
Other: Placebo SC
Placebo SC
Experimental: Denosumab 120 mg SC and Placebo IV
Denosumab 120 mg SC + Placebo IV over at least 15 minutes Q4W (n = 760)
Drug: Denosumab
Denosumab 120 mg SC
Other: Placebo IV
Placebo IV

Primary Outcome Measures :
  1. Time to the first on-study skeletal related event (SRE) (non-inferiority test) [ Time Frame: Approximately 50 months ]
    Until approximately 676 subjects have experienced at least one on-study SRE (anticipated to be approximately 50 months).

Secondary Outcome Measures :
  1. Time to the first-and-subsequent SRE (superiority test, using multiple event analysis) [ Time Frame: Approximately 50 months ]
    Until approximately 676 subjects have experienced at least one on-study SRE (anticipated to be approximately 50 months)

  2. Time to the first on-study SRE (superiority test) [ Time Frame: Approximately 50 months ]
    Until approximately 676 subjects have experienced at least one on-study SRE (anticipated to be approximately 50 months)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01345019

  Show 309 Study Locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
Study Director: MD Amgen

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01345019     History of Changes
Other Study ID Numbers: 20090482
First Posted: April 29, 2011    Key Record Dates
Last Update Posted: December 22, 2017
Last Verified: December 2017

Keywords provided by Amgen:
zoledronic acid
hematologic malignancies
skeletal-related event
blood cancer
lytic bone lesions
bone metastases
spinal cord compression
radiation to bone
surgery to bone
Neoplasms, Plasma Cell
Neoplasm Metastasis
Bone Neoplasms
Bone Marrow Diseases
Blood Protein Disorders
Hematologic Diseases
multiple myeloma
Neoplastic Processes
Bone Diseases
Bone Density Conservation Agents

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm Metastasis
Bone Diseases
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Musculoskeletal Diseases
Zoledronic acid
Bone Density Conservation Agents
Physiological Effects of Drugs