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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01345019




Registration number
NCT01345019
Ethics application status
Date submitted
28/04/2011
Date registered
29/04/2011

Titles & IDs
Public title
Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Patients With Multiple Myeloma
Scientific 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
Secondary ID [1] 0 0
2010-020454-34
Secondary ID [2] 0 0
20090482
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Hematologic Malignancies 0 0
Multiple Myeloma 0 0
Oncology 0 0
Bone Metastases 0 0
Multiple Myeloma Bone Lesions 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Denosumab
Treatment: Drugs - Zoledronic acid
Treatment: Drugs - Placebo to Denosumab
Treatment: Drugs - Placebo to zoledronic acid
Treatment: Drugs - Denosumab (for the open-label treatment phase)

Active comparator: Zoledronic acid - Zoledronic acid 4 mg intravenously plus placebo to denosumab subcutaniously (SC) once every 4 weeks (Q4W) in the double-blind treatment period (Since denosumab was determined to have a positive benefit:risk profile in the primary analysis of the study, per protocol, participants who were still undergoing Q4W scheduled assessments were offered open-label denosumab 120 mg SC Q4W for up to 2 years)

Experimental: Denosumab - Denosumab 120 mg subcutaniously (SC) plus placebo to zoledronic acid intravenously once every 4 weeks (Q4W) in the double-blind treatment period (Since denosumab was determined to have a positive benefit:risk profile in the primary analysis of the study, per protocol, participants who were still undergoing Q4W scheduled assessments were offered open-label denosumab 120 mg SC Q4W for up to 2 years)


Treatment: Drugs: Denosumab
Administered by subcutaneous injection once every 4 weeks.

Treatment: Drugs: Zoledronic acid
Administered by intravenous infusion over 15 minutes once every 4 weeks

Treatment: Drugs: Placebo to Denosumab
Administered by subcutaneous injection once every 4 weeks.

Treatment: Drugs: Placebo to zoledronic acid
Administered by intravenous infusion over 15 minutes once every 4 weeks

Treatment: Drugs: Denosumab (for the open-label treatment phase)
Administered by subcutaneous injection once every 4 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to First On-study Skeletal Related Event
Timepoint [1] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
Primary outcome [2] 0 0
Percentage of Participants With an On-study Skeletal Related Event
Timepoint [2] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
Primary outcome [3] 0 0
Kaplan-Meier Estimate of Percentage of Participants With an On-study Skeletal Related Event
Timepoint [3] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively. The Kaplan-Meier estimate at weeks 25, 49 and 109 is reported.
Secondary outcome [1] 0 0
Time to First On-study Skeletal Related Event - Superiority Analysis
Timepoint [1] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
Secondary outcome [2] 0 0
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events Per Patient
Timepoint [2] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
Secondary outcome [3] 0 0
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events
Timepoint [3] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
Secondary outcome [4] 0 0
Overall Survival
Timepoint [4] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.
Secondary outcome [5] 0 0
Percentage of Participants Who Died
Timepoint [5] 0 0
From randomization until the primary analysis data cut-off date of 19 July 2016 (per protocol); median time on study was 17.6 and 17.3 months in each treatment group respectively.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,VIC
Recruitment hospital [1] 0 0
Research Site - Liverpool
Recruitment hospital [2] 0 0
Research Site - Tweed Heads
Recruitment hospital [3] 0 0
Research Site - Douglas
Recruitment hospital [4] 0 0
Research Site - South Brisbane
Recruitment hospital [5] 0 0
Research Site - Hobart
Recruitment hospital [6] 0 0
Research Site - Clayton
Recruitment hospital [7] 0 0
Research Site - Epping
Recruitment hospital [8] 0 0
Research Site - Malvern
Recruitment hospital [9] 0 0
Research Site - Parkville
Recruitment hospital [10] 0 0
Research Site - Prahran
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [3] 0 0
4814 - Douglas
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3076 - Epping
Recruitment postcode(s) [8] 0 0
3144 - Malvern
Recruitment postcode(s) [9] 0 0
3050 - Parkville
Recruitment postcode(s) [10] 0 0
3181 - Prahran
Recruitment outside Australia
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United States of America
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Torino
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Udine
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Aichi
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Akita
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Chiba
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Fukuoka
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Anyang
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Busan
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Gwangju
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Incheon
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Seoul
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Kaunas
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Lithuania
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Penza
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Country [182] 0 0
Slovakia
State/province [182] 0 0
Nove Zamky
Country [183] 0 0
Spain
State/province [183] 0 0
Andalucía
Country [184] 0 0
Spain
State/province [184] 0 0
Baleares
Country [185] 0 0
Spain
State/province [185] 0 0
Castilla León
Country [186] 0 0
Spain
State/province [186] 0 0
Cataluña
Country [187] 0 0
Spain
State/province [187] 0 0
Comunidad Valenciana
Country [188] 0 0
Spain
State/province [188] 0 0
Galicia
Country [189] 0 0
Spain
State/province [189] 0 0
País Vasco
Country [190] 0 0
Spain
State/province [190] 0 0
Madrid
Country [191] 0 0
Switzerland
State/province [191] 0 0
Chur
Country [192] 0 0
Switzerland
State/province [192] 0 0
Zurich
Country [193] 0 0
Taiwan
State/province [193] 0 0
Changhua
Country [194] 0 0
Taiwan
State/province [194] 0 0
Kaohsiung
Country [195] 0 0
Taiwan
State/province [195] 0 0
Taichung
Country [196] 0 0
Taiwan
State/province [196] 0 0
Tainan
Country [197] 0 0
Taiwan
State/province [197] 0 0
Taipei
Country [198] 0 0
Taiwan
State/province [198] 0 0
Taoyuan
Country [199] 0 0
Turkey
State/province [199] 0 0
Adana
Country [200] 0 0
Turkey
State/province [200] 0 0
Ankara
Country [201] 0 0
Turkey
State/province [201] 0 0
Istanbul
Country [202] 0 0
Turkey
State/province [202] 0 0
Izmir
Country [203] 0 0
Ukraine
State/province [203] 0 0
Cherkasy
Country [204] 0 0
Ukraine
State/province [204] 0 0
Dnipropetrovsk
Country [205] 0 0
Ukraine
State/province [205] 0 0
Ivano-Frankivsk
Country [206] 0 0
Ukraine
State/province [206] 0 0
Khmelnitskiy
Country [207] 0 0
Ukraine
State/province [207] 0 0
Kyiv
Country [208] 0 0
Ukraine
State/province [208] 0 0
Lviv
Country [209] 0 0
Ukraine
State/province [209] 0 0
Poltava
Country [210] 0 0
United Kingdom
State/province [210] 0 0
Harrow
Country [211] 0 0
United Kingdom
State/province [211] 0 0
Inverness
Country [212] 0 0
United Kingdom
State/province [212] 0 0
Leeds
Country [213] 0 0
United Kingdom
State/province [213] 0 0
London
Country [214] 0 0
United Kingdom
State/province [214] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Daiichi Sankyo
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.