Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02412878




Registration number
NCT02412878
Ethics application status
Date submitted
6/04/2015
Date registered
9/04/2015
Date last updated
23/09/2022

Titles & IDs
Public title
Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
Scientific title
A Randomized, Open-label, Phase 3 Study in Subjects With Relapsed and Refractory Multiple Myeloma Receiving Carfilzomib in Combination With Dexamethasone, Comparing Once-weekly Versus Twice-weekly Carfilzomib Dosing
Secondary ID [1] 0 0
2014-005325-12
Secondary ID [2] 0 0
CFZ014
Universal Trial Number (UTN)
Trial acronym
ARROW
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Carfilzomib
Treatment: Drugs - Dexamethasone

Experimental: Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone - Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter).

Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.

Experimental: Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone - Participants received carfilzomib administered by IV infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter).

Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.


Treatment: Drugs: Carfilzomib
Carfilzomib was administered as an IV infusion

Treatment: Drugs: Dexamethasone
Commercially available dexamethasone was obtained by the investigational site.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival
Timepoint [1] 0 0
From randomization until the data cut-off date of 15 June 2017; median (minimum, maximum) follow-up time for PFS was 12.0 (0, 20) and 12.6 (0, 19) months in each treatment group respectively.
Secondary outcome [1] 0 0
Overall Response Rate
Timepoint [1] 0 0
Disease response was assessed every 28 days until progressive disease, up to the data cut-off date of 15 June 2017; median time on follow-up was 12.0 and 12.6 months in each treatment group respectively.
Secondary outcome [2] 0 0
Overall Survival
Timepoint [2] 0 0
From randomization until the data cut-off date of 15 June 2017; median (minimum, maximum) follow-up time for OS was 12.6 (0, 20) and 13.2 (0, 19) months in each treatment group respectively.
Secondary outcome [3] 0 0
Number of Participants With Adverse Events (AEs)
Timepoint [3] 0 0
From first dose of study drug up to 30 days after last dose, up to the end of study; median (minimum, maximum) duration of treatment was 29.1 (0.1, 156.3) weeks and 38.0 (0.1, 158.3) weeks in each treatment group respectively.
Secondary outcome [4] 0 0
Plasma Carfilzomib Concentration During Cycle 2
Timepoint [4] 0 0
Cycle 2 day 1 predose, 15 minutes after the start of infusion (once-weekly carfilzomib only), end of infusion, and 30 minutes after the end of infusion

Eligibility
Key inclusion criteria
Key

1. Relapsed multiple myeloma
2. Refractory multiple myeloma defined as meeting 1 or more of the following:

* Nonresponsive to most recent therapy (stable disease only or PD while on treatment), or
* Disease progression within 60 days of discontinuation from most recent therapy
3. At least 2 but no more than 3 prior therapies for multiple myeloma
4. Prior exposure to an immunomodulatory agent (IMiD)
5. Prior exposure to a proteasome inhibitor (PI)
6. Documented response of at least partial response (PR) to 1 line of prior therapy
7. Measurable disease with at least 1 of the following assessed within the 21 days prior to randomization:

* Serum M-protein = 0.5 g/dL
* Urine M-protein = 200 mg/24 hours
* In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
9. Left ventricular ejection fraction (LVEF) = 40% within the 21 days prior to randomization
10. Adequate organ and bone marrow function within the 21 days prior to randomization defined by:

* Bilirubin < 1.5 times the upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN
* Absolute neutrophil count (ANC) = 1000/mm³ (screening ANC should be independent of growth factor support for = 1 week)
* Hemoglobin = 8.0 g/dL (Use of erythropoietic stimulating factors and red blood cell [RBC] transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.)
* Platelet count = 50,000/mm³ (= 30,000/mm³ if myeloma involvement in the bone marrow is > 50%. Subjects should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count.)
* Calculated or measured creatinine clearance (CrCl) of = 30 mL/min

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Waldenström macroglobulinemia
2. Multiple myeloma of Immunoglobin M (IgM) subtype
3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
4. Plasma cell leukemia (> 2.0 × 10?/L circulating plasma cells by standard differential)
5. Myelodysplastic syndrome
6. Second malignancy within the past 5 years except:

* Adequately treated basal cell or squamous cell skin cancer
* Carcinoma in situ of the cervix
* Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
* Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)
* Treated medullary or papillary thyroid cancer
* Similar condition with an expectation of > 95% five-year disease-free survival
7. History of or current amyloidosis
8. Cytotoxic chemotherapy within the 28 days prior to randomization
9. Immunotherapy within the 21 days prior to randomization
10. Glucocorticoid therapy within the 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or 1000 mg prednisone
11. Radiation therapy:

* Focal therapy within the 7 days prior to randomization
* Extended field therapy within the 21 days prior to randomization
12. Prior treatment with either carfilzomib or oprozomib
13. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
14. Contraindication to dexamethasone or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment
15. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 6 months prior to enrollment
16. Active infection within the 14 days prior to randomization requiring systemic antibiotics
17. Pleural effusions requiring thoracentesis within the 14 days prior to randomization
18. Ascites requiring paracentesis within the 14 days prior to randomization
19. Ongoing graft-versus-host disease
20. Uncontrolled hypertension or uncontrolled diabetes despite medication
21. Significant neuropathy (= Grade 3) within the 14 days prior to randomization
22. Known cirrhosis

Study design
Purpose of the study
Treatment
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
Open (masking not used)
Who is / are masked / blinded?



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
9/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/01/2019
Sample size
Target
Accrual to date
Final
478
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - Darlinghurst
Recruitment hospital [2] 0 0
Research Site - Tweed Heads
Recruitment hospital [3] 0 0
Research Site - Waratah
Recruitment hospital [4] 0 0
Research Site - Box Hill
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Belgium
State/province [7] 0 0
Antwerpen
Country [8] 0 0
Belgium
State/province [8] 0 0
Brugge
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussel
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles
Country [11] 0 0
Belgium
State/province [11] 0 0
Ghent
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Newfoundland and Labrador
Country [16] 0 0
Canada
State/province [16] 0 0
Nova Scotia
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
Czechia
State/province [19] 0 0
Brno
Country [20] 0 0
Czechia
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Hradec Kralove
Country [21] 0 0
Czechia
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Olomouc
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Czechia
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Ostrava-Poruba
Country [23] 0 0
Czechia
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Praha 10
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Czechia
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Praha
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Denmark
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Aalborg
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Denmark
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Copenhagen
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Denmark
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Odense C
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Denmark
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Vejle
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Finland
State/province [29] 0 0
Helsinki
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Finland
State/province [30] 0 0
Tampere
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Finland
State/province [31] 0 0
Turku
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France
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Bayonne
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France
State/province [33] 0 0
Brest
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France
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Dijon
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France
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Nantes Cedex 1
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France
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Nimes cedex 09
Country [37] 0 0
France
State/province [37] 0 0
Paris
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France
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Pierre-Benite cedex
Country [39] 0 0
France
State/province [39] 0 0
Rennes
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France
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Tours Cedex 1
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Germany
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Köln
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Germany
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Leipzig
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Germany
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München
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Germany
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Rostock
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Germany
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Tubingen
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Greece
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Athens
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Greece
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Patra
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Gyula
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Hungary
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Kaposvar
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Italy
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Ancona
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Italy
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Bologna
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Italy
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Brescia
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Italy
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Cagliari
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Italy
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Catania
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Italy
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Firenze
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Italy
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Genova
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Italy
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Napoli
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Italy
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Pavia
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Italy
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Piacenza
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Italy
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Pisa
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Italy
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Roma
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Italy
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Torino
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Japan
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Aichi
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Japan
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Fukuoka
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Japan
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Gifu
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Gunma
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Hokkaido
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Kanagawa
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Kyoto
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Japan
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Miyagi
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Okayama
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Tochigi
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Japan
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Tokyo
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Japan
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Fukuoka-shi
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Japan
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Nagoya-shi
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Japan
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Niigata-shi
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Japan
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Tokushima-shi
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New Zealand
State/province [82] 0 0
Christchurch
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New Zealand
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Otahuhu, Auckland
Country [84] 0 0
Norway
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Oslo
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Norway
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Trondheim
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Poland
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Brzozow
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Poland
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Chorzow
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Poland
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Katowice
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Poland
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Krakow
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Poland
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Lodz
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Poland
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Olsztyn
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Poland
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Poznan
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Poland
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Torun
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Poland
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Warszawa
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Poland
State/province [95] 0 0
Wroclaw
Country [96] 0 0
Romania
State/province [96] 0 0
Brazov
Country [97] 0 0
Romania
State/province [97] 0 0
Bucharest
Country [98] 0 0
Spain
State/province [98] 0 0
Andalucía
Country [99] 0 0
Spain
State/province [99] 0 0
Aragón
Country [100] 0 0
Spain
State/province [100] 0 0
Baleares
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Spain
State/province [101] 0 0
Castilla León
Country [102] 0 0
Spain
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Cataluña
Country [103] 0 0
Spain
State/province [103] 0 0
Navarra
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Spain
State/province [104] 0 0
Madrid
Country [105] 0 0
Sweden
State/province [105] 0 0
Goteborg
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Sweden
State/province [106] 0 0
Helsingborg
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Sweden
State/province [107] 0 0
Lund
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Sweden
State/province [108] 0 0
Stockholm
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Sweden
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Uddevalla
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United Kingdom
State/province [110] 0 0
Bournemouth
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
State/province [113] 0 0
Nottingham
Country [114] 0 0
United Kingdom
State/province [114] 0 0
Sheffield
Country [115] 0 0
United Kingdom
State/province [115] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

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

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02412878