Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
NCT ID: NCT02412878
Last Updated: 2022-09-23
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
478 participants
INTERVENTIONAL
2015-09-09
2019-01-07
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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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.
Carfilzomib
Carfilzomib was administered as an IV infusion
Dexamethasone
Commercially available dexamethasone was obtained by the investigational site.
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.
Carfilzomib
Carfilzomib was administered as an IV infusion
Dexamethasone
Commercially available dexamethasone was obtained by the investigational site.
Interventions
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Carfilzomib
Carfilzomib was administered as an IV infusion
Dexamethasone
Commercially available dexamethasone was obtained by the investigational site.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
Exclusion Criteria
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 × 10⁹/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
18 Years
ALL
No
Sponsors
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Amgen
INDUSTRY
Responsible Party
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Principal Investigators
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MD
Role: STUDY_DIRECTOR
Amgen
Locations
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Research Site
Scottsdale, Arizona, United States
Mayo Clinic
Scottsdale, Arizona, United States
Research Site
Bethesda, Maryland, United States
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States
Research Site
Rockville, Maryland, United States
Maryland Oncology Hematology, P.A
Rockville, Maryland, United States
Research Site
Hackensack, New Jersey, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Research Site
New York, New York, United States
Research Site
Pittsburgh, Pennsylvania, United States
Research Site
Tyler, Texas, United States
Blood and Cancer Center of East Texas
Tyler, Texas, United States
Research Site
Darlinghurst, New South Wales, Australia
Research Site
Tweed Heads, New South Wales, Australia
Research Site
Waratah, New South Wales, Australia
Research Site
Box Hill, Victoria, Australia
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Antwerp, , Belgium
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Bruges, , Belgium
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Brussels, , Belgium
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Brussels, , Belgium
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Ghent, , Belgium
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Leuven, , Belgium
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Calgary, Alberta, Canada
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Kelowna, British Columbia, Canada
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Vancouver, British Columbia, Canada
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St. John's, Newfoundland and Labrador, Canada
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Halifax, Nova Scotia, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Brno, , Czechia
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Hradec Králové, , Czechia
Research Site
Olomouc, , Czechia
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Ostrava-Poruba, , Czechia
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Prague, , Czechia
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Prague, , Czechia
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Aalborg, , Denmark
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Copenhagen, , Denmark
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Odense C, , Denmark
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Vejle, , Denmark
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Helsinki, , Finland
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Tampere, , Finland
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Turku, , Finland
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Bayonne, , France
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Brest, , France
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Dijon, , France
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Nantes, , France
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Nîmes, , France
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Paris, , France
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Pierre-Bénite, , France
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Rennes, , France
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Tours, , France
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Cologne, , Germany
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Leipzig, , Germany
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München, , Germany
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Rostock, , Germany
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Tübingen, , Germany
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Athens, , Greece
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Athens, , Greece
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Pátrai, , Greece
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Budapest, , Hungary
Research Site
Debrecen, , Hungary
Research Site
Gyula, , Hungary
Research Site
Kaposvár, , Hungary
Research Site
Ancona, , Italy
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Bologna, , Italy
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Brescia, , Italy
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Cagliari, , Italy
Research Site
Catania, , Italy
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Florence, , Italy
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Genova, , Italy
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Napoli, , Italy
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Pavia, , Italy
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Piacenza, , Italy
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Pisa, , Italy
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Roma, , Italy
Research Site
Roma, , Italy
Research Site
Torino, , Italy
Research Site
Toyohashi, Aichi-ken, Japan
Research Site
Fukuoka, Fukuoka, Japan
Research Site
Ogaki-shi, Gifu, Japan
Research Site
Maebashi, Gunma, Japan
Research Site
Shibukawa-shi, Gunma, Japan
Research Site
Sapporo, Hokkaido, Japan
Research Site
Isehara-shi, Kanagawa, Japan
Research Site
Kyoto, Kyoto, Japan
Research Site
Sendai, Miyagi, Japan
Research Site
Okayama, Okayama-ken, Japan
Research Site
Suita-shi, Osaka, Japan
Research Site
Kawagoe-shi, Saitama, Japan
Research Site
Utsunomiya, Tochigi, Japan
Research Site
Chuo-ku, Tokyo, Japan
Research Site
Koto-ku, Tokyo, Japan
Research Site
Shibuya-ku, Tokyo, Japan
Research Site
Tachikawa-shi, Tokyo, Japan
Research Site
Fukuoka, , Japan
Research Site
Nagoya, , Japan
Research Site
Niigata, , Japan
Research Site
Tokushima, , Japan
Research Site
Christchurch, , New Zealand
Research Site
Otahuhu, Auckland, , New Zealand
Research Site
Oslo, , Norway
Research Site
Trondheim, , Norway
Research Site
Brzozów, , Poland
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Chorzów, , Poland
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Katowice, , Poland
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Krakow, , Poland
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Lodz, , Poland
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Olsztyn, , Poland
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Poznan, , Poland
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Torun, , Poland
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Warsaw, , Poland
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Wroclaw, , Poland
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Brasov, , Romania
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Bucharest, , Romania
Research Site
Seville, Andalusia, Spain
Research Site
Zaragoza, Aragon, Spain
Research Site
Palma de Mallorca, Balearic Islands, Spain
Research Site
Salamanca, Castille and León, Spain
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Badalona, Catalonia, Spain
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Barcelona, Catalonia, Spain
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Girona, Catalonia, Spain
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Pamplona, Navarre, Spain
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Madrid, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Gothenburg, , Sweden
Research Site
Helsingborg, , Sweden
Research Site
Lund, , Sweden
Research Site
Stockholm, , Sweden
Research Site
Stockholm, , Sweden
Research Site
Uddevalla, , Sweden
Research Site
Bournemouth, , United Kingdom
Research Site
London, , United Kingdom
Research Site
London, , United Kingdom
Research Site
Manchester, , United Kingdom
Research Site
Nottingham, , United Kingdom
Research Site
Sheffield, , United Kingdom
Research Site
Wolverhampton, , United Kingdom
Countries
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References
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Moreau P, Mateos MV, Berenson JR, Weisel K, Lazzaro A, Song K, Dimopoulos MA, Huang M, Zahlten-Kumeli A, Stewart AK. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study. Lancet Oncol. 2018 Jul;19(7):953-964. doi: 10.1016/S1470-2045(18)30354-1. Epub 2018 Jun 1.
Facon T, Niesvizky R, Mateos MV, Siegel D, Rosenbaum C, Bringhen S, Weisel K, Ho PJ, Ludwig H, Kumar S, Wang K, Obreja M, Yang Z, Klippel Z, Mezzi K, Goldrick A, Tekle C, Dimopoulos MA. Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.
Dimopoulos MA, Niesvizky R, Weisel K, Siegel DS, Hajek R, Mateos MV, Cavo M, Huang M, Zahlten-Kumeli A, Moreau P. Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis. Blood Cancer J. 2020 Mar 9;10(3):35. doi: 10.1038/s41408-020-0300-y.
Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.
Moreau P, Kumar S, Boccia R, Iida S, Goldschmidt H, Cocks K, Trigg A, Zahlten-Kumeli A, Yucel E, Panjabi SS, Dimopoulos M. Convenience, satisfaction, health-related quality of life of once-weekly 70 mg/m2 vs. twice-weekly 27 mg/m2 carfilzomib (randomized A.R.R.O.W. study). Leukemia. 2019 Dec;33(12):2934-2946. doi: 10.1038/s41375-019-0480-2. Epub 2019 May 15.
Kumar SK, Majer I, Panjabi S, Medhekar R, Campioni M, Dimopoulos MA. Cost-effectiveness of once weekly carfilzomib 70 mg/m2 plus dexamethasone in patients with relapsed and refractory multiple myeloma in the United States. Expert Rev Hematol. 2020 Jun;13(6):687-696. doi: 10.1080/17474086.2020.1746639. Epub 2020 Apr 6.
Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, Zahlten-Kumeli A, Sersch MA, Li J, Huang M, Lee JH. Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials. Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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AmgenTrials clinical trials website
Other Identifiers
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2014-005325-12
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
20140355
Identifier Type: OTHER
Identifier Source: secondary_id
CFZ014
Identifier Type: -
Identifier Source: org_study_id
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