Multiple MyelomaPhase 3ARROWNCT02412878
Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma
A Phase 3 study testing Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Amgen at 140 sites in 20 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Carfilzomib and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 478 participants
- Where
- 140 sitesin 20 countries
- Study dates
- 9 Sep 2015to 7 Jan 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
- 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)
Show all 21Show fewer
- 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:
- 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
Who cannot join
- 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:
Show all 30Show fewer
- 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
- Glucocorticoid therapy within the 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or 1000 mg prednisone
- Radiation therapy:
- Focal therapy within the 7 days prior to randomization
- Extended field therapy within the 21 days prior to randomization
- Prior treatment with either carfilzomib or oprozomib
- Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
- 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
- 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
- Active infection within the 14 days prior to randomization requiring systemic antibiotics
- Pleural effusions requiring thoracentesis within the 14 days prior to randomization
- Ascites requiring paracentesis within the 14 days prior to randomization
- Ongoing graft-versus-host disease
- Uncontrolled hypertension or uncontrolled diabetes despite medication
- Significant neuropathy (≥ Grade 3) within the 14 days prior to randomization
- Known cirrhosis
Trial locations and contacts
140 sites in 20 countries.
140 sites in 20 countries
Japan21 sites
Research Site
Chuo-ku, Tokyo, 104-0045
Research Site
Fukuoka, Fukuoka, 812-8582
Research Site
Fukuoka, 811-1395
Research Site
Isehara-shi, Kanagawa, 259-1193
Research Site
Kawagoe-shi, Saitama, 350-8550
Research Site
Koto-ku, Tokyo, 135-8550
Research Site
Kyoto, Kyoto, 602-8566
Research Site
Maebashi, Gunma, 371-8511
Research Site
Nagoya, 467-8602
Research Site
Niigata, 951-8566
Research Site
Ogaki-shi, Gifu, 503-8502
Research Site
Okayama, Okayama-ken, 701-1192
Research Site
Sapporo, Hokkaido, 060-8543
Research Site
Sendai, Miyagi, 980-8574
Research Site
Shibukawa-shi, Gunma, 377-8511
Research Site
Shibuya-ku, Tokyo, 150-8935
Research Site
Suita-shi, Osaka, 565-0871
Research Site
Tachikawa-shi, Tokyo, 190-0014
Research Site
Tokushima, 770-8539
Research Site
Toyohashi, Aichi-ken, 441-8570
Research Site
Utsunomiya, Tochigi, 320-0834
Italy14 sites
Research Site
Ancona, 60126
Research Site
Bologna, 40138
Research Site
Brescia, 25123
Research Site
Cagliari, 09121
Research Site
Catania, 95124
Research Site
Florence, 50134
Research Site
Genova, 16132
Research Site
Naples, 80131
Research Site
Pavia, 27100
Research Site
Piacenza, 29100
Research Site
Pisa, 56100
Research Site
Roma, 00161
Research Site
Roma, 00168
Research Site
Torino, 10126
United States12 sites
Research Site
Bethesda, Maryland, 20817
Center for Cancer and Blood Disorders
Bethesda, Maryland
Research Site
Hackensack, New Jersey, 07601
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey
Research Site
New York, New York, 10021
Research Site
Pittsburgh, Pennsylvania, 15224
Research Site
Rockville, Maryland, 20850
Maryland Oncology Hematology, P.A
Rockville, Maryland
Research Site
Scottsdale, Arizona, 85259-5499
Mayo Clinic
Scottsdale, Arizona
Research Site
Tyler, Texas, 75701
Blood and Cancer Center of East Texas
Tyler, Texas
Spain11 sites
Research Site
Badalona, Catalonia, 08916
Research Site
Barcelona, Catalonia, 08036
Research Site
Girona, Catalonia, 17007
Research Site
Madrid, 28034
Research Site
Madrid, 28040
Research Site
Madrid, 28041
Research Site
Palma de Mallorca, Balearic Islands, 07010
Research Site
Pamplona, Navarre, 31008
Research Site
Salamanca, Castille and León, 37007
Research Site
Seville, Andalusia, 41013
Research Site
Zaragoza, Aragon, 50012
Poland10 sites
Research Site
Brzozów, 36-200
Research Site
Chorzów, 41-500
Research Site
Katowice, 40-032
Research Site
Krakow, 31-501
Research Site
Lodz, 93-510
Research Site
Olsztyn, 10-228
Research Site
Poznan, 60-569
Research Site
Torun, 87-100
Research Site
Warsaw, 02-106
Research Site
Wroclaw, 50-367
Canada9 sites
Research Site
Calgary, Alberta, T2N 2T9
Research Site
Halifax, Nova Scotia, B3H 2Y9
Research Site
Kelowna, British Columbia, V1Y 5L3
Research Site
Montreal, Quebec, H4J 1C5
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Québec, Quebec, G1J 1Z4
Research Site
St. John's, Newfoundland and Labrador, A1B 3V6
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Vancouver, British Columbia, V5Z 1M9
France9 sites
Research Site
Bayonne, 64109
Research Site
Brest, 29609
Research Site
Dijon, 21000
Research Site
Nantes, 44093
Research Site
Nîmes, 30029
Research Site
Paris, 75012
Research Site
Pierre-Bénite, 69495
Research Site
Rennes, 35033
Research Site
Tours, 37044
United Kingdom7 sites
Research Site
Bournemouth, BH7 7DW
Research Site
London, EC1A 7BE
Research Site
London, NW1 2PG
Research Site
Manchester, M13 9WL
Research Site
Nottingham, NG5 1PB
Research Site
Sheffield, S10 2JF
Research Site
Wolverhampton, WV10 0QP
Belgium6 sites
Research Site
Antwerp, 2060
Research Site
Bruges, 8000
Research Site
Brussels, 1090
Research Site
Brussels, 1200
Research Site
Ghent, 9000
Research Site
Leuven, 3000
Czechia6 sites
Research Site
Brno, 625 00
Research Site
Hradec Králové, 500 05
Research Site
Olomouc, 775 20
Research Site
Ostrava-Poruba, 708 52
Research Site
Prague, 100 34
Research Site
Prague, 128 08
Sweden6 sites
Research Site
Gothenburg, 413 45
Research Site
Helsingborg, 251 87
Research Site
Lund, 221 85
Research Site
Stockholm, 141 86
Research Site
Stockholm, 171 76
Research Site
Uddevalla, 451 80
Germany5 sites
Research Site
Cologne, 50937
Research Site
Leipzig, 04103
Research Site
München, 81241
Research Site
Rostock, 18057
Research Site
Tübingen, 72076
Australia4 sites
Research Site
Box Hill, Victoria, 3128
Research Site
Darlinghurst, New South Wales, 2010
Research Site
Tweed Heads, New South Wales, 2485
Research Site
Waratah, New South Wales, 2298
Denmark4 sites
Research Site
Aalborg, 9000
Research Site
Copenhagen, 2100
Research Site
Odense C, 5000
Research Site
Vejle, 7100
Hungary4 sites
Research Site
Budapest, 1097
Research Site
Debrecen, 4032
Research Site
Gyula, 5700
Research Site
Kaposvár, 7400
Finland3 sites
Research Site
Helsinki, 00290
Research Site
Tampere, 33521
Research Site
Turku, 20520
Greece3 sites
Research Site
Athens, 10676
Research Site
Athens, 11528
Research Site
Pátrai, 26504
New Zealand2 sites
Research Site
Christchurch, 8011
Research Site
Otahuhu, Auckland, 1640
About this study
Official 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
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).
- Conditions
- Multiple Myeloma
- Being tested
- Carfilzomib, Dexamethasone
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called PR-171, PR171, Kyprolis® (carfilzomib) for Injection
Carfilzomib was administered as an IV infusion
DexamethasoneDrug
Commercially available dexamethasone was obtained by the investigational site.
| Study group | Role | What they receive |
|---|---|---|
| Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone | Experimental | 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. Receives: Drug: Carfilzomib; Drug: Dexamethasone |
| Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone | Experimental | 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. Receives: Drug: Carfilzomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 evaluated according to the IMWG-URC using a validated computer algorithm. Overall response rate was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).
sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).
CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM biopsy; VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
Measured: 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
Overall Survival (OS) was defined as the time from randomization to death due to any cause.
Median overall survival was derived using the Kaplan-Meier method; participants still alive were censored at the date last known to be alive.
Measured: 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)
The severity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03, where where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal.
Treatment-related adverse events are adverse events considered related to at least 1 investigational product by the investigator, including those with unknown relationship.
Measured: 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
Concentrations of carfilzomib in plasma were measured using a validated assay method. The lower limit of quantification was 0.100 ng/mL.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2015 (estimated)
- Study start9 Sep 2015
- Primary completion15 Jun 2017
- Study completion7 Jan 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 (7)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 478 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02412878
- Sponsor's protocol ID
- CFZ014
- Other IDs
- 2014-005325-12, 20140355, 2014
- Acronym
- ARROW
- Status last verified
- Sep 2022
- First submitted
- 6 Apr 2015
- Last updated
- 23 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 29866475Facon 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.
PubMed 33166401Dimopoulos 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.
PubMed 32152297Moreau 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.
PubMed 32108443Moreau 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.
PubMed 31092895Kumar 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.
PubMed 32249621Dimopoulos 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.
PubMed 31388932
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02412878
- Acronym / sponsor ID
- ARROW / CFZ014
- Conditions
- Multiple Myeloma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 478 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 9 Sep 2015 (actual)
- Primary completion
- 15 Jun 2017 (actual)
- Study completion
- 7 Jan 2019 (actual)
- First posted
- 9 Apr 2015 (estimated)
- Results
- Posted 13 Dec 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 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone | Experimental | Drug: Carfilzomib, Drug: DexamethasoneParticipants 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 | Experimental | Drug: Carfilzomib, Drug: DexamethasoneParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Relapsed multiple myeloma
- Refractory multiple myeloma defined as meeting 1 or more of the following:
- 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)
Key exclusion criteria (30 listed)
- 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
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 |
|---|---|---|
| CarfilzomibAlso: PR-171, PR171, Kyprolis® (carfilzomib) for InjectionCarfilzomib was administered as an IV infusion | Drug | Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone, Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone |
| DexamethasoneCommercially available dexamethasone was obtained by the investigational site. | Drug | Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone, Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone |
Primary outcome
Progression Free Survival
Time frame: 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.
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.
4 secondary outcomes
Overall Response Rate
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29866475Moreau 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.
- Background: PubMed 33166401Facon 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.
- Background: PubMed 32152297Dimopoulos 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.
- Background: PubMed 32108443Moreau 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.
- Background: PubMed 31092895Moreau 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.
- Background: PubMed 32249621Kumar 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.
- Derived from this study: PubMed 31388932Dimopoulos 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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
140 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Amgen at 140 sites in 20 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 21 inclusion and 30 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 23 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 140 sites in Japan, Italy, United States, Spain, Poland and 15 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 13 Dec 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?
Progression Free Survival (time frame: 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.). 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 NCT02412878, which also lists 7 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 23 Sep 2022.