Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
ARROW
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
3 other identifiers
interventional
478
20 countries
140
Brief Summary
The purpose of the study is to compare the progression-free survival (PFS) of once-weekly carfilzomib dosing in combination with dexamethasone to twice-weekly carfilzomib dosing in combination with dexamethasone in adults with relapsed and refractory multiple myeloma, previously treated with bortezomib and an immunomodulatory agent (IMiD).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 multiple-myeloma
Started Sep 2015
Shorter than P25 for phase_3 multiple-myeloma
140 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 6, 2015
CompletedFirst Posted
Study publicly available on registry
April 9, 2015
CompletedStudy Start
First participant enrolled
September 9, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 15, 2017
CompletedResults Posted
Study results publicly available
December 13, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 7, 2019
CompletedSeptember 23, 2022
September 1, 2022
1.8 years
April 6, 2015
October 24, 2018
September 9, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Progression Free Survival
Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Disease status was assessed at a central laboratory with serum and urine protein electrophoresis, immunofixation, serum-free light chain (SFLC) assay, bone marrow sample evaluation, serum calcium, plasmacytoma evaluation, and skeletal survey. Response and disease progression were determined using a validated computer algorithm based on the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). Median PFS was derived using the Kaplan-Meier method; participants still alive with no disease progression were censored at the time of their last disease assessment.
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 Outcomes (4)
Overall Response Rate
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.
Overall Survival
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.
Number of Participants With Adverse Events (AEs)
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.
Plasma Carfilzomib Concentration During Cycle 2
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
Study Arms (2)
Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
EXPERIMENTALParticipants 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.
Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone
EXPERIMENTALParticipants 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.
Interventions
Carfilzomib was administered as an IV infusion
Commercially available dexamethasone was obtained by the investigational site.
Eligibility Criteria
You may qualify if:
- Relapsed multiple myeloma
- 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
- At least 2 but no more than 3 prior therapies for multiple myeloma
- Prior exposure to an immunomodulatory agent (IMiD)
- Prior exposure to a proteasome inhibitor (PI)
- Documented response of at least partial response (PR) to 1 line of prior therapy
- 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
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Left ventricular ejection fraction (LVEF) ≥ 40% within the 21 days prior to randomization
- Adequate organ and bone marrow function within the 21 days prior to randomization defined by:
- +6 more criteria
You may not qualify if:
- Waldenström macroglobulinemia
- Multiple myeloma of Immunoglobin M (IgM) subtype
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (\> 2.0 × 10⁹/L circulating plasma cells by standard differential)
- Myelodysplastic syndrome
- 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
- History of or current amyloidosis
- Cytotoxic chemotherapy within the 28 days prior to randomization
- Immunotherapy within the 21 days prior to randomization
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (140)
Research Site
Scottsdale, Arizona, 85259-5499, United States
Mayo Clinic
Scottsdale, Arizona, United States
Research Site
Bethesda, Maryland, 20817, United States
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States
Research Site
Rockville, Maryland, 20850, United States
Maryland Oncology Hematology, P.A
Rockville, Maryland, United States
Research Site
Hackensack, New Jersey, 07601, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Research Site
New York, New York, 10021, United States
Research Site
Pittsburgh, Pennsylvania, 15224, United States
Research Site
Tyler, Texas, 75701, United States
Blood and Cancer Center of East Texas
Tyler, Texas, United States
Research Site
Darlinghurst, New South Wales, 2010, Australia
Research Site
Tweed Heads, New South Wales, 2485, Australia
Research Site
Waratah, New South Wales, 2298, Australia
Research Site
Box Hill, Victoria, 3128, Australia
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Antwerp, 2060, Belgium
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Bruges, 8000, Belgium
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Brussels, 1090, Belgium
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Brussels, 1200, Belgium
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Ghent, 9000, Belgium
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Leuven, 3000, Belgium
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Calgary, Alberta, T2N 2T9, Canada
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Kelowna, British Columbia, V1Y 5L3, Canada
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Vancouver, British Columbia, V5Z 1M9, Canada
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St. John's, Newfoundland and Labrador, A1B 3V6, Canada
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Halifax, Nova Scotia, B3H 2Y9, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Montreal, Quebec, H4J 1C5, Canada
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Québec, Quebec, G1J 1Z4, Canada
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Brno, 625 00, Czechia
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Hradec Králové, 500 05, Czechia
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Olomouc, 775 20, Czechia
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Ostrava-Poruba, 708 52, Czechia
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Prague, 100 34, Czechia
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Prague, 128 08, Czechia
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Aalborg, 9000, Denmark
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Copenhagen, 2100, Denmark
Research Site
Odense C, 5000, Denmark
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Vejle, 7100, Denmark
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Helsinki, 00290, Finland
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Tampere, 33521, Finland
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Turku, 20520, Finland
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Bayonne, 64109, France
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Brest, 29609, France
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Dijon, 21000, France
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Nantes, 44093, France
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Nîmes, 30029, France
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Paris, 75012, France
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Pierre-Bénite, 69495, France
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Rennes, 35033, France
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Tours, 37044, France
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Cologne, 50937, Germany
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Leipzig, 04103, Germany
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München, 81241, Germany
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Rostock, 18057, Germany
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Tübingen, 72076, Germany
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Athens, 10676, Greece
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Athens, 11528, Greece
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Pátrai, 26504, Greece
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Budapest, 1097, Hungary
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Debrecen, 4032, Hungary
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Gyula, 5700, Hungary
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Kaposvár, 7400, Hungary
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Ancona, 60126, Italy
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Bologna, 40138, Italy
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Brescia, 25123, Italy
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Cagliari, 09121, Italy
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Catania, 95124, Italy
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Florence, 50134, Italy
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Genova, 16132, Italy
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Napoli, 80131, Italy
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Pavia, 27100, Italy
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Piacenza, 29100, Italy
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Pisa, 56100, Italy
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Roma, 00161, Italy
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Roma, 00168, Italy
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Torino, 10126, Italy
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Toyohashi, Aichi-ken, 441-8570, Japan
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Fukuoka, Fukuoka, 812-8582, Japan
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Ogaki-shi, Gifu, 503-8502, Japan
Research Site
Maebashi, Gunma, 371-8511, Japan
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Shibukawa-shi, Gunma, 377-8511, Japan
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Sapporo, Hokkaido, 060-8543, Japan
Research Site
Isehara-shi, Kanagawa, 259-1193, Japan
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Kyoto, Kyoto, 602-8566, Japan
Research Site
Sendai, Miyagi, 980-8574, Japan
Research Site
Okayama, Okayama-ken, 701-1192, Japan
Research Site
Suita-shi, Osaka, 565-0871, Japan
Research Site
Kawagoe-shi, Saitama, 350-8550, Japan
Research Site
Utsunomiya, Tochigi, 320-0834, Japan
Research Site
Chuo-ku, Tokyo, 104-0045, Japan
Research Site
Koto-ku, Tokyo, 135-8550, Japan
Research Site
Shibuya-ku, Tokyo, 150-8935, Japan
Research Site
Tachikawa-shi, Tokyo, 190-0014, Japan
Research Site
Fukuoka, 811-1395, Japan
Research Site
Nagoya, 467-8602, Japan
Research Site
Niigata, 951-8566, Japan
Research Site
Tokushima, 770-8539, Japan
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Christchurch, 8011, New Zealand
Research Site
Otahuhu, Auckland, 1640, New Zealand
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Oslo, 0372, Norway
Research Site
Trondheim, 7006, Norway
Research Site
Brzozów, 36-200, Poland
Research Site
Chorzów, 41-500, Poland
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Katowice, 40-032, Poland
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Krakow, 31-501, Poland
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Lodz, 93-510, Poland
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Olsztyn, 10-228, Poland
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Poznan, 60-569, Poland
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Torun, 87-100, Poland
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Warsaw, 02-106, Poland
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Wroclaw, 50-367, Poland
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Brasov, 500152, Romania
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Bucharest, 022328, Romania
Research Site
Seville, Andalusia, 41013, Spain
Research Site
Zaragoza, Aragon, 50012, Spain
Research Site
Palma de Mallorca, Balearic Islands, 07010, Spain
Research Site
Salamanca, Castille and León, 37007, Spain
Research Site
Badalona, Catalonia, 08916, Spain
Research Site
Barcelona, Catalonia, 08036, Spain
Research Site
Girona, Catalonia, 17007, Spain
Research Site
Pamplona, Navarre, 31008, Spain
Research Site
Madrid, 28034, Spain
Research Site
Madrid, 28040, Spain
Research Site
Madrid, 28041, Spain
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Gothenburg, 413 45, Sweden
Research Site
Helsingborg, 251 87, Sweden
Research Site
Lund, 221 85, Sweden
Research Site
Stockholm, 141 86, Sweden
Research Site
Stockholm, 171 76, Sweden
Research Site
Uddevalla, 451 80, Sweden
Research Site
Bournemouth, BH7 7DW, United Kingdom
Research Site
London, EC1A 7BE, United Kingdom
Research Site
London, NW1 2PG, United Kingdom
Research Site
Manchester, M13 9WL, United Kingdom
Research Site
Nottingham, NG5 1PB, United Kingdom
Research Site
Sheffield, S10 2JF, United Kingdom
Research Site
Wolverhampton, WV10 0QP, United Kingdom
Related Publications (7)
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.
PMID: 29866475BACKGROUNDFacon 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.
PMID: 33166401BACKGROUNDDimopoulos 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.
PMID: 32152297BACKGROUNDMoreau 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.
PMID: 32108443BACKGROUNDMoreau 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.
PMID: 31092895BACKGROUNDKumar 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.
PMID: 32249621BACKGROUNDDimopoulos 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.
PMID: 31388932DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Amgen Inc.
Study Officials
- STUDY DIRECTOR
MD
Amgen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 6, 2015
First Posted
April 9, 2015
Study Start
September 9, 2015
Primary Completion
June 15, 2017
Study Completion
January 7, 2019
Last Updated
September 23, 2022
Results First Posted
December 13, 2018
Record last verified: 2022-09