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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01345019
First received: April 28, 2011
Last updated: August 17, 2016
Last verified: August 2016

April 28, 2011
August 17, 2016
May 2012
July 2016   (final data collection date for primary outcome measure)
Time to the first on-study skeletal related event (SRE) (non-inferiority test) [ Time Frame: Approximately 50 months ] [ Designated as safety issue: No ]
Until approximately 676 subjects have experienced at least one on-study SRE (anticipated to be approximately 50 months).
Time to the first on-study skeletal related event (SRE) (non-inferiority test) [ Time Frame: until approximately 800 subjects have experienced at least one on-study SRE (anticipated to be approximately 48 months) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01345019 on ClinicalTrials.gov Archive Site
  • Time to the first-and-subsequent SRE (superiority test, using multiple event analysis) [ Time Frame: Approximately 50 months ] [ Designated as safety issue: No ]
    Until approximately 676 subjects have experienced at least one on-study SRE (anticipated to be approximately 50 months)
  • Time to the first on-study SRE (superiority test) [ Time Frame: Approximately 50 months ] [ Designated as safety issue: No ]
    Until approximately 676 subjects have experienced at least one on-study SRE (anticipated to be approximately 50 months)
  • Time to the first on-study SRE (superiority test) [ Time Frame: until approximately 800 subjects have experienced at least one on-study SRE (anticipated to be approximately 48 months) ] [ Designated as safety issue: No ]
  • Time to the first-and-subsequent SRE (superiority test, using multiple event analysis) [ Time Frame: until approximately 800 subjects have experienced at least one on-study SRE (anticipated to be approximately 48 months) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Subjects With Multiple Myeloma
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
  • Cancer
  • Hematologic Malignancies
  • Multiple Myeloma
  • Oncology
  • Bone Metastases
  • Multiple Myeloma Bone Lesions
  • Drug: Denosumab
    Denosumab 120 mg SC
  • Drug: Zoledronic acid
    Zoledronic acid 4 mg (adjusted for renal function) IV over at least 15 minutes Q4W (n = 760)
  • 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)
    Intervention: Drug: Zoledronic acid
  • Experimental: Denosumab 120 mg SC and Placebo IV
    Denosumab 120 mg SC + Placebo IV over at least 15 minutes Q4W (n = 760)
    Intervention: Drug: Denosumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1718
March 2019
July 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Austria,   Bulgaria,   Canada,   Czech Republic,   France,   Germany,   Greece,   Hong Kong,   Hungary,   Ireland,   Italy,   Japan,   Korea, Republic of,   Lithuania,   Malaysia,   New Zealand,   Poland,   Portugal,   Russian Federation,   Singapore,   Slovakia,   Spain,   Switzerland,   Taiwan,   Turkey,   Ukraine,   United Kingdom
 
NCT01345019
20090482
Yes
Not Provided
Not Provided
Amgen
Amgen
Daiichi Sankyo Inc.
Study Director: MD Amgen
Amgen
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP