CancerPhase 3NCT01345019
Denosumab Compared to Zoledronic Acid in the Treatment of Bone Disease in Patients With Multiple Myeloma
A Phase 3 study testing Denosumab, Zoledronic acid and Denosumab (for the open-label treatment phase) in people with Cancer and Hematologic Malignancies, run by Amgen at 309 sites in 29 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Hematologic Malignancies, Multiple Myeloma
- What is being tested?
- Denosumab, Zoledronic acid and Denosumab (for the open-label treatment phase)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,718 participants
- Where
- 309 sitesin 29 countries
- Study dates
- 17 May 2012to 29 Mar 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
309 sites in 29 countries.
309 sites in 29 countries
United States79 sites
Research Site
Aberdeen, South Dakota, 57401
Research Site
Ames, Iowa, 50010
Research Site
Anaheim, California, 92801
Research Site
Anderson, Indiana, 46016
Research Site
Baltimore, Maryland, 21204
Research Site
Baltimore, Maryland, 21229
Research Site
Baltimore, Maryland, 21237
Research Site
Bethesda, Maryland, 20817
Research Site
Billings, Montana, 59101
Research Site
Bismarck, North Dakota, 58501
Research Site
Boston, Massachusetts, 02114
Research Site
Boston, Massachusetts, 02215
Research Site
Boynton Beach, Florida, 33426
Research Site
Boynton Beach, Florida, 33435
Research Site
Campbell, California, 95008
Research Site
Charleston, South Carolina, 29406
Research Site
Charleston, South Carolina, 29414
Research Site
Chicago, Illinois, 60612
Research Site
Christiansburg, Virginia, 24073
Research Site
Columbus, Georgia, 31904
Research Site
Danvers, Massachusetts, 01923
Research Site
Detroit, Michigan, 48201
Research Site
Encinitas, California, 92024
Research Site
Fairhaven, Massachusetts, 02719
Research Site
Fayetteville, Arkansas, 72703
Research Site
Fayetteville, North Carolina, 28304
Research Site
Fort Wayne, Indiana, 46845
Research Site
Fresno, California, 93720
Research Site
Goldsboro, North Carolina, 27534
Research Site
Greenville, South Carolina, 29615
Research Site
Hackensack, New Jersey, 07601
Research Site
Hershey, Pennsylvania, 17033
Research Site
High Point, North Carolina, 27262
Research Site
Houston, Texas, 77030
Research Site
Indianapolis, Indiana, 46202
Research Site
Iowa City, Iowa, 52242
Research Site
Jackson, Mississippi, 39216
Research Site
Jacksonville, Florida, 32256
Research Site
Joliet, Illinois, 60435
Research Site
Lake Success, New York, 11042
Research Site
Lansing, Michigan, 48910
Research Site
Lincoln, Nebraska, 68506
Research Site
Lubbock, Texas, 79415
Research Site
Maywood, Illinois, 60153
Research Site
Memphis, Tennessee, 38120
Research Site
Minocqua, Wisconsin, 54548
Research Site
Morgantown, West Virginia, 26506
Research Site
New Orleans, Louisiana, 70121
Research Site
New York, New York, 10021
Research Site
Niles, Illinois, 60714
Research Site
North Las Vegas, Nevada, 89086
Research Site
Oklahoma City, Oklahoma, 73120-8345
Research Site
Omaha, Nebraska, 68198
Research Site
Paducah, Kentucky, 42003
Research Site
Philadelphia, Pennsylvania, 19106
Research Site
Philadelphia, Pennsylvania, 19140
Research Site
Philadelphia, Pennsylvania, 19141
Research Site
Pleasant Hill, California, 94523
Research Site
Rapid City, South Dakota, 57701
Research Site
Rochester, New York, 14621
Research Site
Salt Lake City, Utah, 84106
Research Site
Santa Barbara, California, 93105
Research Site
Santa Maria, California, 93454
Research Site
Savannah, Georgia, 31405
Research Site
Scarborough, Maine, 04074
Research Site
Sioux Falls, South Dakota, 57105
Research Site
Skokie, Illinois, 60076
Research Site
Skokie, Illinois, 60077
Research Site
Spokane, Washington, 99208
Research Site
Springfield, Missouri, 65806
Research Site
Stamford, Connecticut, 06902
Research Site
Tacoma, Washington, 98405
Research Site
Tucson, Arizona, 85704
Research Site
Washington D.C., District of Columbia, 20007
Research Site
Washington D.C., District of Columbia, 20010
Research Site
Watertown, South Dakota, 57201
Research Site
Wauwatosa, Wisconsin, 53226
Research Site
West Reading, Pennsylvania, 19611
Research Site
Westminster, Maryland, 21157
France25 sites
Research Site
Amiens, 80054
Research Site
Avignon, 84902
Research Site
Créteil, 94010
Research Site
Le Kremlin-Bicêtre, 94270
Research Site
Le Mans, 72000
Research Site
Le Mans, 72037
Research Site
Lille, 59037
Research Site
Lyon Cédex 3, 69437
Research Site
Marseille, 13273
Research Site
Marseille, 13385
Research Site
Nantes, 44035
Research Site
Nice, 06202
Research Site
Paris, 75010
Research Site
Paris, 75013
Research Site
Paris, 75015
Research Site
Paris, 75571
Research Site
Paris, 75679
Research Site
Pessac, 33604
Research Site
Pierre-Bénite, 69495
Research Site
Pontoise, 95301
Research Site
Reims, 51056
Research Site
Rouen, 76038
Research Site
Saint-Quentin, 02321
Research Site
Strasbourg, 67000
Research Site
Villefranche-sur-Saône, 69400
Italy21 sites
Research Site
Ancona, 60126
Research Site
Bari, 70124
Research Site
Brescia, 25125
Research Site
Busto Arsizio, 21052
Research Site
Catania, 95124
Research Site
Florence, 50134
Research Site
Genova, 16132
Research Site
Messina, 98125
Research Site
Milan, 20153
Research Site
Naples, 80131
Research Site
Naples, 80136
Research Site
Novara, 28100
Research Site
Palermo, 90146
Research Site
Pescara, 65124
Research Site
Pisa, 56127
Research Site
Roma, 00144
Research Site
Roma, 00161
Research Site
Rozzano MI, 20089
Research Site
Torino, 10126
Research Site
Udine, 33100
Research Site
Vimercate MB, 20871
Japan18 sites
Research Site
Akita, Akita, 010-8543
Research Site
Fukuoka, Fukuoka, 814-0180
Research Site
Fukuyama-shi, Hiroshima, 720-0001
Research Site
Gifu, Gifu, 501-1194
Research Site
Kamogawa-shi, Chiba, 296-8602
Research Site
Kawagoe-shi, Saitama, 350-8550
Research Site
Kobe, Hyōgo, 650-0047
Research Site
Kumamoto, Kumamoto, 860-0008
Research Site
Kyoto, Kyoto, 603-8151
Research Site
Maebashi, Gunma, 371-8511
Research Site
Nagoya, Aichi-ken, 457-8510
Research Site
Ogaki-shi, Gifu, 503-8502
Research Site
Okayama, Okayama-ken, 701-1192
Research Site
Shibukawa-shi, Gunma, 377-8511
Research Site
Shibuya-ku, Tokyo, 150-8935
Research Site
Shinjuku-ku, Tokyo, 162-8655
Research Site
Tokushima, Tokushima, 770-8503
Research Site
Toyama, Toyama, 930-8550
Canada17 sites
Research Site
Barrie, Ontario, L4M 6M2
Research Site
Burnaby, British Columbia, V5G 2X6
Research Site
Laval, Quebec, H7M 3L9
Research Site
Moncton, New Brunswick, E1C 6Z8
Research Site
Montreal, Quebec, H1T 2M4
Research Site
Montreal, Quebec, H4J 1C5
Research Site
Newmarket, Ontario, L3Y 2P9
Research Site
Québec, Quebec, G1R 2J6
Research Site
Sault Ste. Marie, Ontario, P6B 0A8
Research Site
St. John's, Newfoundland and Labrador, A1B 3V6
Research Site
Toronto, Ontario, M2K 1E1
Research Site
Toronto, Ontario, M3M 0B2
Research Site
Toronto, Ontario, M5B 1W8
Research Site
Toronto, Ontario, M6R 1B5
Research Site
Trois-Rivières, Quebec, G8Z 3R9
Research Site
Windsor, Ontario, N8W 2X3
Research Site
Winnipeg, Manitoba, R3E 0V9
Russia14 sites
Research Site
Dzerzhinsk, 606019
Research Site
Moscow, 115478
Research Site
Nizhny Novgorod, 603126
Research Site
Novosibirsk, 630051
Research Site
Penza, 440071
Research Site
Petrozavodsk, 185019
Research Site
Saint Petersburg, 193312
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197110
Research Site
Saint Petersburg, 198205
Research Site
Samara, 443099
Research Site
Saratov, 410012
Research Site
Volgograd, 400138
Research Site
Yekaterinburg, 620102
South Korea11 sites
Research Site
Anyang, 431-070
Research Site
Busan, 602-739
Research Site
Daegu, 700-721
Research Site
Daejeon, 301-721
Research Site
Gwangju, 519-763
Research Site
Incheon, 405-760
Research Site
Seoul, 110-744
Research Site
Seoul, 120-752
Research Site
Seoul, 135-710
Research Site
Seoul, 137-701
Research Site
Seoul, 158-710
Spain11 sites
Research Site
Badalona, Catalonia, 08916
Research Site
Barcelona, Catalonia, 08036
Research Site
Donostia / San Sebastian, Basque Country, 20014
Research Site
Madrid, 28006
Research Site
Madrid, 28034
Research Site
Ourense, Galicia, 32005
Research Site
Palma de Mallorca, Balearic Islands, 07198
Research Site
Salamanca, Castille and León, 37007
Research Site
Seville, Andalusia, 41013
Research Site
Valencia, Valencia, 46017
Research Site
Valencia, Valencia, 46026
Australia10 sites
Research Site
Clayton, Victoria, 3168
Research Site
Douglas, Queensland, 4814
Research Site
Epping, Victoria, 3076
Research Site
Hobart, Tasmania, 7000
Research Site
Liverpool, New South Wales, 2170
Research Site
Malvern, Victoria, 3144
Research Site
Parkville, Victoria, 3050
Research Site
Prahran, Victoria, 3181
Research Site
South Brisbane, Queensland, 4101
Research Site
Tweed Heads, New South Wales, 2485
Germany9 sites
Research Site
Bonn, 53127
Research Site
Chemnitz, 09113
Research Site
Cologne, 50924
Research Site
Essen, 45239
Research Site
Hamburg, 20246
Research Site
Kassel, 34125
Research Site
Leipzig, 04103
Research Site
Münster, 48149
Research Site
Regensburg, 93049
Austria7 sites
Research Site
Graz, 8036
Research Site
Innsbruck, 6020
Research Site
Krems, 3500
Research Site
Salzburg, 5020
Research Site
Vienna, 1090
Research Site
Vienna, 1140
Research Site
Wels, 4600
Bulgaria7 sites
Research Site
Pleven, 5800
Research Site
Plovdiv, 4002
Research Site
Sofia, 1407
Research Site
Sofia, 1431
Research Site
Sofia, 1606
Research Site
Sofia, 1756
Research Site
Varna, 9010
Greece7 sites
Research Site
Athens, 11525
Research Site
Athens, 11527
Research Site
Athens, 11528
Research Site
Heraklion, 71110
Research Site
Pátrai, 26500
Research Site
Piraeus, 18537
Research Site
Thessaloniki, 57010
Hungary7 sites
Research Site
Budapest, 1083
Research Site
Budapest, 1097
Research Site
Debrecen, 4032
Research Site
Győr, 9024
Research Site
Gyula, 5700
Research Site
Kaposvár, 7400
Research Site
Szeged, 6725
Poland7 sites
Research Site
Legnica, 59-220
Research Site
Lublin, 20-081
Research Site
Słupsk, 76-200
Research Site
Torun, 87-100
Research Site
Warsaw, 02-097
Research Site
Warsaw, 02-776
Research Site
Wroclaw, 53-439
Taiwan7 sites
Research Site
Changhua, 50006
Research Site
Kaohsiung City, 83301
Research Site
Taichung, 40447
Research Site
Taichung, 407
Research Site
Tainan, 70403
Research Site
Taipei, 10002
Research Site
Taoyuan, 33305
Ukraine7 sites
Research Site
Cherkasy, 18009
Research Site
Dnipropetrovsk, 49102
Research Site
Ivano-Frankivsk, 76008
Research Site
Khmelnitskiy, 29000
Research Site
Kyiv, 04107
Research Site
Lviv, 79031
Research Site
Poltava, 36024
United Kingdom6 sites
Research Site
Harrow, HA1 3UJ
Research Site
Inverness, IV2 3UJ
Research Site
Leeds, LS9 7TF
Research Site
London, NW3 2QG
Research Site
London, SW17 0RE
Research Site
Oxford, OX3 7LJ
Czechia5 sites
Research Site
Brno, 625 00
Research Site
Ostrava-Poruba, 708 52
Research Site
Pilsen, 304 60
Research Site
Prague, 100 34
Research Site
Prague, 128 08
Ireland5 sites
Research Site
Dublin, 24
Research Site
Dublin, 7
Research Site
Dublin, 8
Research Site
Limerick
Research Site
Tullamore
Portugal5 sites
Research Site
Braga, 4710-243
Research Site
Coimbra, 3000-075
Research Site
Lisbon, 1169-050
Research Site
Matosinhos Municipality, 4464-513
Research Site
Porto, 4200-072
Turkey (Türkiye)5 sites
Research Site
Adana, 01330
Research Site
Ankara, 06100
Research Site
Ankara, 06500
Research Site
Istanbul, 34452
Research Site
Izmir, 35340
Malaysia4 sites
Research Site
Ampang, 68000
Research Site
George Town, Pulau Pinang, 10990
Research Site
Ipoh, Perak, 30990
Research Site
Kuching, Sarawak, 93586
Singapore3 sites
Research Site
Singapore, 119228
Research Site
Singapore, 169856
Research Site
Singapore, 308433
Slovakia3 sites
Research Site
Bratislava, 851 07
Research Site
Nitra, 950 01
Research Site
Nové Zámky, 940 34
Switzerland3 sites
Research Site
Chur, 7000
Research Site
Zurich, 8032
Research Site
Zurich, 8038
New Zealand2 sites
Research Site
Christchurch, 8011
Research Site
Grafton, Auckland, 1023
About this study
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
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.
- Conditions
- Cancer, Hematologic Malignancies, Multiple Myeloma, Oncology, Bone Metastases, Multiple Myeloma Bone Lesions
- Being tested
- Denosumab, Zoledronic acid, Placebo to Denosumab, Placebo to zoledronic acid, Denosumab (for the open-label treatment phase)
- Keywords
- zoledronic acid, hematologic malignancies, SRE, skeletal-related event, blood cancer, lytic bone lesions, bone metastases, myeloma, fractures, spinal cord compression, radiation to bone, surgery to bone, bisphosphonates, Neoplasms, Plasma Cell, Paraproteinemias, Neoplasms, Neoplasm Metastasis, Bone Neoplasms, Bone Marrow Diseases, Blood Protein Disorders
- Medical subject headings
- Neoplasms, Hematologic Neoplasms, Multiple Myeloma, Neoplasms, Plasma Cell, Fractures, Bone, Spinal Cord Compression, Paraproteinemias, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called XGEVA®, AMG 162
Administered by subcutaneous injection once every 4 weeks.
Zoledronic acidDrug
Also called Zometa®
Administered by intravenous infusion over 15 minutes once every 4 weeks
Placebo to DenosumabDrug
Administered by subcutaneous injection once every 4 weeks.
Placebo to zoledronic acidDrug
Administered by intravenous infusion over 15 minutes once every 4 weeks
Denosumab (for the open-label treatment phase)Drug
Also called XGEVA®, AMG 162
Administered by subcutaneous injection once every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic acid | Active comparator | 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) Receives: Drug: Zoledronic acid; Drug: Placebo to Denosumab; Drug: Denosumab (for the open-label treatment phase) |
| Denosumab | Experimental | 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) Receives: Drug: Denosumab; Drug: Placebo to zoledronic acid; Drug: Denosumab (for the open-label treatment phase) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to First On-study Skeletal Related Event
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. If there was no known event, and the participant was monitored for any one of the four SRE components, time to first on-study SRE was censored at the end of the treatment phase date or the primary analysis data cut-off date, whichever came first.
Measured: 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.
Percentage of Participants With an On-study Skeletal Related Event
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
Measured: 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.
Kaplan-Meier Estimate of Percentage of Participants With an On-study Skeletal Related Event
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
Measured: 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 outcomes (5)
Time to First On-study Skeletal Related Event - Superiority Analysis
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. If there was no known event, and the participant was monitored for any one of the four SRE components, time to first on-study SRE was censored at the end of the treatment phase date or the primary analysis data cut-off date, whichever came first.
Measured: 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.
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events Per Patient
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. Time to a subsequent SRE is defined, similarly to the time to first on-study SRE, as the time interval from the randomization date to the date of a subsequent occurrence of on-study SRE, which had to be at least 21 days after the previous SRE.
A multiple event analysis was used, which accounts for both the absolute number of SREs and for the time between two consecutive events, and therefore, provides a more sensitive assessment of the risk of experiencing an SRE. The average number of events per patient is reported.
Measured: 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.
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. Time to a subsequent SRE is defined, similarly to the time to first on-study SRE, as the time interval from the randomization date to the date of a subsequent occurrence of on-study SRE, which had to be at least 21 days after the previous SRE.
A multiple event analysis was used, which accounts for both the absolute number of SREs and for the time between two consecutive events, and therefore, provides a more sensitive assessment of the risk of experiencing an SRE. The total number of events is reported.
Measured: 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.
Overall Survival
Overall survival was defined as the time interval (in days) from the randomization date to the date of death. If a participant was still alive at the primary analysis data cut-off date or was lost to follow-up by the primary analysis data cut-off date, survival time was censored at their last contact date or the primary analysis data cut-off date, whichever was first.
Measured: 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.
Percentage of Participants Who Died
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2011 (estimated)
- Study start17 May 2012
- Primary completion19 Jul 2016
- Study completion29 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,718 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01345019
- Sponsor's protocol ID
- 20090482
- Other IDs
- 2010-020454-34
- Status last verified
- Nov 2022
- First submitted
- 28 Apr 2011
- Last updated
- 8 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Publications
Raje N, Roodman GD, Willenbacher W, Shimizu K, Garcia-Sanz R, Terpos E, Kennedy L, Sabatelli L, Intorcia M, Hechmati G. A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America. J Med Econ. 2018 May;21(5):525-536. doi: 10.1080/13696998.2018.1445634. Epub 2018 Mar 5.
PubMed 29480139Raje N, Terpos E, Willenbacher W, Shimizu K, Garcia-Sanz R, Durie B, Legiec W, Krejci M, Laribi K, Zhu L, Cheng P, Warner D, Roodman GD. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018 Mar;19(3):370-381. doi: 10.1016/S1470-2045(18)30072-X. Epub 2018 Feb 9.
PubMed 29429912Huang SY, Yoon SS, Shimizu K, Chng WJ, Chang CS, Wong RS, Gao S, Wang Y, Gordon SW, Glennane A, Min CK. Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis. Adv Ther. 2020 Jul;37(7):3404-3416. doi: 10.1007/s12325-020-01395-x. Epub 2020 Jun 10.
PubMed 32524500Terpos E, Raje N, Croucher P, Garcia-Sanz R, Leleu X, Pasteiner W, Wang Y, Glennane A, Canon J, Pawlyn C. Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study. Blood Adv. 2021 Feb 9;5(3):725-736. doi: 10.1182/bloodadvances.2020002378.
PubMed 33560384
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01345019
- Acronym / sponsor ID
- 20090482
- Conditions
- Cancer, Hematologic Malignancies, Multiple Myeloma, Oncology, Bone Metastases, Multiple Myeloma Bone Lesions
- Keywords
- zoledronic acid, hematologic malignancies, SRE, skeletal-related event, blood cancer, lytic bone lesions, bone metastases, myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,718 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo
- Study start
- 17 May 2012 (actual)
- Primary completion
- 19 Jul 2016 (actual)
- Study completion
- 29 Mar 2019 (actual)
- First posted
- 29 Apr 2011 (estimated)
- Results
- Posted 7 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Zoledronic acid | Active comparator | Drug: Zoledronic acid, Drug: Placebo to Denosumab, Drug: Denosumab (for the open-label treatment phase)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) |
| Denosumab | Experimental | Drug: Denosumab, Drug: Placebo to zoledronic acid, Drug: Denosumab (for the open-label treatment phase)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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (25 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: XGEVA®, AMG 162Administered by subcutaneous injection once every 4 weeks. | Drug | Denosumab |
| Zoledronic acidAlso: Zometa®Administered by intravenous infusion over 15 minutes once every 4 weeks | Drug | Zoledronic acid |
| Placebo to DenosumabAdministered by subcutaneous injection once every 4 weeks. | Drug | Zoledronic acid |
| Placebo to zoledronic acidAdministered by intravenous infusion over 15 minutes once every 4 weeks | Drug | Denosumab |
| Denosumab (for the open-label treatment phase)Also: XGEVA®, AMG 162Administered by subcutaneous injection once every 4 weeks. | Drug | Denosumab, Zoledronic acid |
Primary outcome
Time to First On-study Skeletal Related Event
Time frame: 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.
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression. Time to first on-study SRE is defined as the time interval (in days) from the randomization date to the date of first occurrence of on-study SRE. If there was no known event, and the participant was monitored for any one of the four SRE components, time to first on-study SRE was censored at the end of the treatment phase date or the primary analysis data cut-off date, whichever came first.
Percentage of Participants With an On-study Skeletal Related Event
Time frame: 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.
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
Kaplan-Meier Estimate of Percentage of Participants With an On-study Skeletal Related Event
Time frame: 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.
A skeletal-related event (SRE) is defined as one of the following: pathologic fracture (vertebral or non-vertebral), radiation therapy to bone (including the use of radioisotopes), surgery to bone, or spinal cord compression.
5 secondary outcomes
Time to First On-study Skeletal Related Event - Superiority Analysis
Time frame: 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.
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events Per Patient
Time frame: 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.
Time to First and Subsequent On-Study Skeletal Related Event - Number of Events
Time frame: 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.
Overall Survival
Time frame: 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.
Percentage of Participants Who Died
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29480139Raje N, Roodman GD, Willenbacher W, Shimizu K, Garcia-Sanz R, Terpos E, Kennedy L, Sabatelli L, Intorcia M, Hechmati G. A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America. J Med Econ. 2018 May;21(5):525-536. doi: 10.1080/13696998.2018.1445634. Epub 2018 Mar 5.
- Background: PubMed 29429912Raje N, Terpos E, Willenbacher W, Shimizu K, Garcia-Sanz R, Durie B, Legiec W, Krejci M, Laribi K, Zhu L, Cheng P, Warner D, Roodman GD. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018 Mar;19(3):370-381. doi: 10.1016/S1470-2045(18)30072-X. Epub 2018 Feb 9.
- Background: PubMed 32524500Huang SY, Yoon SS, Shimizu K, Chng WJ, Chang CS, Wong RS, Gao S, Wang Y, Gordon SW, Glennane A, Min CK. Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis. Adv Ther. 2020 Jul;37(7):3404-3416. doi: 10.1007/s12325-020-01395-x. Epub 2020 Jun 10.
- Background: PubMed 33560384Terpos E, Raje N, Croucher P, Garcia-Sanz R, Leleu X, Pasteiner W, Wang Y, Glennane A, Canon J, Pawlyn C. Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study. Blood Adv. 2021 Feb 9;5(3):725-736. doi: 10.1182/bloodadvances.2020002378.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Related trials for Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
309 sites in 29 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Denosumab, Zoledronic acid and Denosumab (for the open-label treatment phase) in people with Cancer and Hematologic Malignancies, run by Amgen at 309 sites in 29 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 309 sites in United States, France, Italy, Japan, Canada and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to First On-study Skeletal Related Event (time frame: 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 study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01345019, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.