Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma

Multiple Myeloma Clinical Trial

— CLARION  

Official title:

A Randomized, Open-label Phase 3 Study of Carfilzomib, Melphalan, and Prednisone Versus Bortezomib, Melphalan, and Prednisone in Transplant-ineligible Patients With Newly Diagnosed Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01818752
• Other study ID #: 2012-005
• Secondary ID: 2012-005283-9720
• Status: Completed
• Phase: Phase 3
• Start date: July 8, 2013
• Est. completion date: November 4, 2016

Study information

• Verified date: August 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective was to compare the progression-free survival of transplant ineligible patients newly diagnosed with multiple myeloma who were treated with carfilzomib, melphalan and prednisone (CMP) or with Velcade® (bortezomib), melphalan and prednisone (VMP).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 955
• Est. completion date: November 4, 2016
• Est. primary completion date: July 15, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Newly diagnosed symptomatic multiple myeloma (per International Myeloma Working Group [IMWG] diagnostic criteria)

2. Transplant ineligibility

3. Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to randomization):

• Serum M-protein = 0.5 g/dL, or

• Urine M-protein = 200 mg/24 hours, or

• In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ratio (SFLC kappa lambda ratio < 0.26 or > 1.65)

4. No prior treatment for multiple myeloma

5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

1. Multiple myeloma of IgM (immunoglobulin M) subtype

2. Glucocorticoid therapy within 14 days prior to randomization that equals or exceeds a cumulative dose of 160 mg of dexamethasone

3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

4. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)

5. Waldenström macroglobulinemia (WM)

6. Known amyloidosis

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Carfilzomib
Carfilzomib was administered over 30 minutes on days 1, 2, 8, 9, 22, 23, 29, and 30 for nine 42-day cycles. Carfilzomib 20 mg/m² IV was administered on days 1 and 2 of cycle 1, followed by escalation to 36 mg/m² IV starting on day 8 of cycle 1.
• Bortezomib
Bortezomib 1.3 mg/m² was administered as a bolus IV injection or as a subcutaneous injection (per investigator's choice, dose modification, or regulatory approval) on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycles 1 to 4, and on days 1, 8, 22, and 29 of cycles 5 to 9.
• Melphalan
Melphalan 9 mg/m² was taken orally on days 1 to 4 of all cycles.
• Prednisone
Prednisone 60 mg/m² was taken orally on days 1 to 4 of all cycles.

Locations

Country	Name	City	State
Argentina	Centro de educacion medica c investigacioncs clinicas "Norberto Quimo' (CEMIC)	Buenos Aires
Argentina	Sanatorio Britanico S.A.	Santa Fe
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Eastern Health - Box Hill Hospital	Box Hill	Victoria
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	St. Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal North Shore Hospital, Haematology Department	New South Wales
Australia	Central Coast Local Health District	North Gosford	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Border Medical Oncology	Wodonga	Victoria
Austria	Medical University of Innsbruck, University Clinic for Internal Medicine V	Innsbruck
Austria	Elisabeth Linz Hospital	Linz
Austria	Vienna Wilhelminen Hospital	Vienna
Belgium	ZNA, Stuivenberg	Antwerp	Antwerpen
Belgium	Saint Joseph Clinic Arlon, Department of Hematology	Arlon	Luxembourg
Belgium	CHR de La Citadelle (ENG: Citadelle Regional Hospital Center)	Liège
Belgium	CHU Mont-Godinne	Yvoir
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Hematology Clinic	Plovdiv
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Oncology and Hematology Clinic	Plovdiv
Bulgaria	Military Medical Academy - Multiprofile Hospital for Active Treatment, Sofia, Hematology and Oncology Clinic	Sofia
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases, Sofia, Hematology Clinic	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment "Sveta Marina", Varna	Varna
Canada	CSSS-Champlain-Charles LeMoyne	Greenfield Park	Quebec
China	307 Hospital of PLA	Beijing
China	Beijing Chao Yang Hospital, Capital Medical University	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University Third Hospital	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Fujian Medical University Union Hospital	Fuzhou City	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	The First Affiliated Hospital of College of Medicine, Zhejiang University - Dr. Jie Jin	Hangzhou	Zhejiang
China	Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai
China	Shanghai Changzheng Hospital	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute on Hematology & Blood Diseases Hospital Chinese Academy of Medical Scicnces & Peking Union Medical University	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	The First Affiliated Hospital of the Fourth Military Medical University of PLA	Xi'an City	Shanxi
Czechia	University Hospital Brno, Department of Internal Hematology and Oncology	Brno
Czechia	University Hospital Brno, Hospital Pharmacy - Department of Dilution of Cytostasis	Brno
Czechia	University Hospital Hradec Kralove	Hradec Kralove
Czechia	University Hospital Olomouc, 3rd Clinic of Internal Medicine, Nephrology, Rheumatology and Endocrinology	Olomouc
Czechia	University Hospital Ostrava, Clinic of Hematooncology of UHO and MFUO	Ostrava
Czechia	General University Hospital Prague, 1st Department of Medicine - Department of Hematology	Prague
Czechia	University Hospital Kralovske Vinohrady - Internal Hematology Clinic	Prague
France	CHU de Caen, Côte de Nacre	Caen Cedex 9
France	CHU Estaing	Clermont-Ferrand
France	UHC Dijon, Children's Hospital	Dijon
France	CHRU Lille Hôpital Claude Huriez	Lille
France	CHRU Hopital Huriez, Departement of Hematology	Lille Cedex
France	Paoli Calmettes Institute, Department ofHematology 2	Marseille cedex
France	Nantes University Hospital Center	Nantes Cedex 1
France	Centre Hospitalier Regional Universitaire de Nimes, Groupe Hospitalo-Universitaire Caremeau	Nimes cedex 9
France	Hopital Saini Louis, Service d'immuno-Hematologie	Paris
France	Hopital Saint Antoine	Paris
France	Hospital Necker	Paris
France	Centre Hospitalier Lyon Sud, Service d'hématologie Clinique	Pierre Bénite, Cedex
France	South Lyon Hospital Center	Pierre Bénite, cedex
France	Hopital Pontchaillou	Rennes Cedex 9
France	Hospital Purpan	Toulouse Cedex 9
France	CHU de Tours Hopital Bretonneau	Tours Cedex 1
Germany	University Hospital Cologne	Cologne	Nordrhein-Westfalen
Germany	Group Practice for Hematology and Oncology	Dresden
Germany	Freiburg University Medical Center	Freiburg	Baden-Wuerttemberg
Germany	Saarland University Hospital	Homburg / Saar	Saarland
Germany	Stiftungsklinikum Mittelrhein GmbH, Clinic of Internal Medicine	Koblenz
Germany	Johannes Gutenberg-University Mainz, Medical Clinic and Policlinic III	Mainz	Rhineland-Palatinate
Germany	Ludwig Maximilians University Hospital - Medical Clinic III	Munich	Bavaria
Germany	Ulm University Hospital, Center for Internal Medicine, Clinic of Internal Medicine III	Ulm	Baden-Wuerttemberg
Greece	Evangelismos Hospital	Athens	Attica
Greece	University of Athens, Alexandra Hospital	Athens
Hungary	National Institute of Oncology, Department of Oncology, Internal Medicine "A" and Hematology	Budapest
Hungary	St. Istvan and St. Laszlo Hospital of Budapest, Department of Haematology and Stem-cell Transplant	Budapest
Hungary	University of Debrecen, Medical and Health Science Center, Institute for Medicine, Chair of Hematology	Debrecen
Hungary	Bekes County Pandy Kalman Hospital 1st Department of Internal Medicine, Hematology	Gyula
Hungary	Kaposi Mor County Teaching Hospital, 2nd Department of Internal Medicine, Hematology	Kaposvar
Hungary	Bacs-Kiskun County Teaching Hospital, II. Department of Internal Medicine	Kecskemet
Hungary	Medical Center of the University of Pecs, 1st Clinic for Internal Medicine	Pecs
Israel	Soroka University Medical Center	Beer-Sheva
Israel	Rambam Medical Center, Department of Hematology	Haifa
Israel	Ein Kerem Hospital, Department of Hematology	Jerusalem
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Italy	Ospedali Riuniti di Ancona Umberto I, G.M. Lancisi, G. Salesi	Ancona
Italy	UO Clinica Ematologica, IRCCS A.O.U. San Martino	Genova	GE
Italy	Maggiore della Carita Hospital of Novara	Novara
Italy	A.O.U. San Luigi Gonzaga	Orbassano	TO
Italy	Local NHS of Piacenza Hospital Guglielmo da Saliceto Department Oncology-Hematology, Unit of Hema	Piacenza
Italy	Ospedale S. Eugenio	Roma
Italy	Policlinico Universitario "Umberto I"	Rome
Italy	AO Città della Salute e della Scienza di Torino, Division of Hematology	Torino
Japan	Kyushu University Hospital	Fukuoka	Fukuoka-Ken
Japan	The Cancer Institute Hospital of Japanese Foundation For Cancer Research	Koto	Tokyo
Japan	University Hospital, Kyoto Prefectural University of Medicine	Kyoto
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	National Hospitalization Organization Kyushu Cancer Center	Minami-ku	Fukuoka
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Ogaki Municipal Hospital	Ogaki	Gifu
Japan	National Hospital Organization Okayama Medical Center	Okayama-city	Okayama
Japan	Sapporo Medical University Hospital	Sapporo-shi	Hokkaidou
Japan	National Center for Global Health and Medicine	Shinjuku	Tokyo
Japan	Osaka University Hospital	Suita	Osaka
Japan	National Hospital Organization Disaster Medical Center	Tachikawa-city	Tokyo
Japan	Tokushima Prefectural Central Hospital	Tokushima
Japan	Japanese Red Cross Medical Center	Tokyo	Shibuya-ku
Japan	Toyohashi Municipal Hospital	Toyohashi	Aichi
Japan	Tochigi Cancer Center	Utsunomiya	Tochigi
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeollanam-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Mexico	Fundacion Centro Oncologieo de Integracion Regional - COIR	Mendoza
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo Leon
Mexico	Consultorio Privado del Dr. Guillermo Jose Ruiz y Arguelles	Puebla
Netherlands	Vrije Universiteit Medisch Centrum (VUMC), Department of Hematology	Amsterdam
Netherlands	St. Antonius Ziekenhuis, Department of Hematology	Nieuwegein
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Isala Clinics in Zwolle, Department of Oncology	Zwolle
New Zealand	Auckland City Hospital	Auckland
New Zealand	North Shore Hospital	Auckland
New Zealand	Canterbury Health Laboratories	Christchurch
New Zealand	Wellington Hospital	Wellington
Poland	Independent Public Healthcare Facility Municipal Hospital Group, Department of Hematology	Chorzow	Slaskie
Poland	Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice	Katowice
Poland	Independent Public Healthcare Facility University Hospital	Krakow
Poland	Nicolaus Copernicus Memorial Provincial Specialist Hospital	Lodz
Poland	Independent Public Teaching Hospital No.1 in Lublin, Dept. of Hematology-Oncology	Lublin
Poland	Independent Public Healthcare Facility of the Ministry of Internal Affairs & Warminsko-Mazurskie Oncology Centre in Olsztyn	Olsztyn	OIsztyn
Poland	Nicolaus Copernicus Municipal Specialist Hospital, Department of Hematology	Torun
Poland	Maria Sklodowska-Curie Institute of Oncology	Warsaw
Romania	Brasov County Emergency Clinical Hospital, Hematology Department	Brasov
Romania	Bucharest Emergency University Hospital, Hematology Department	Bucharest
Romania	Coltea Clinical Hospital, Hematology Department	Bucharest
Romania	Fundeni Clinical Institute, Hematology Department	Bucharest
Romania	"Prof. Dr. Ion Chiricuta" Institut of Oncology, Hematology Department	Cluj-Napoca	Cluj County
Romania	Iasi Regional Institute for Oncology, Medical Hematology Department	Iasi	Iasi County
Romania	Targu-Mures County Emergency Clinical Hospital, Clinic of Hematology and Bone Marrow Transplantation	Targu-Mures
Russian Federation	Arkhangelsk Regional Clinical Hospital, Department of internal diseases #2	Arkhangelsk
Russian Federation	State Medical Institution: First Republican Clinical Hospital under the Ministry of Healthcare of the Republic of Udmurtia	Izhevsk
Russian Federation	City Clinical Hospital N.A.S.P. Botkin, Department of Bone Marrow Transplantation and Intensive Chemotherapy for Patients with Myeloproliferative Disorders	Moscow
Russian Federation	Institution of the Russian Academy of Medical Sciences Russian Oncological Research Center n.a. N.N.Blokhin under the Russian Academy of Medical Sciences	Moscow
Russian Federation	State Medical Institution: Republican Hospital n a.V.A. Baranov, Department of Hematology	Petrozavodsk	Republic Of Karelia
Russian Federation	State Higher Educational Institution St. Petersburg Pavlov State Medical University	Saint Petersburg
Russian Federation	The Federal State Budget Institute The Nikiforov Russian Center of Emergency and Radiation Medicine the Ministry of Russian	Saint Petersburg
Russian Federation	City Clinical Hospital #31, Department of Bone Marrow Transplantation and Intensive Chemotherapy for Patients with Myeloproliferative Disorders	St. Petersburg
Russian Federation	Federal State Institution: Russian Research Institute of Hematology and Blood Transfusion under the Federal Agency for High-Tech Medical Care	St. Petersburg
Singapore	National University Hospital	Singapore
Singapore	OncoCare Cancer Center	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Singapore Oncology Consultants, Gleneagles Hospital	Singapore
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barselona
Spain	Hospital Clinic i Provincial Barcelona	Barcelona
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	University Hospital of Navarra	Pamplona	Navarra
Spain	Hospital Universitario, Salamanca	Salamanca
Spain	Hospital Virgen del Rocio University	Sevilla
Spain	Universitari i Politècnic la Fe de Valencia Consulta Externa de Hematología	Valencia
Spain	Hospital Quiron Zaragoza	Zaragoza
Switzerland	University Hospital Center Vaudois	Lausanne
Switzerland	County Hospital Saint Gallen	Saint Gallen
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Kuohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang-Gung Memorial Hospital, Linkou	Tapei
Turkey	Ankara University Medical Faculty, Cebeci Research and Application Hospital, Hematology Department	Ankara	Cebeci
Turkey	Marmara University Pendik Training and Research Hospital	Istanbul	Pendik
Turkey	Ege University Medical Faculty	Izmir	Bornova
Ukraine	Cherkasy Regional Oncology Center	Cherkasy
Ukraine	Dnipropetrovsk City Multispecialty Clinical Hospital #4, Hematology Centre	Dnipropetrovsk
Ukraine	Kharkiv Regional Clinical Oncology Center, Department of Hematology	Kharkiv
Ukraine	Khmelnytskyi Regional Hospital, Hematology Department	Khmelnytskyi
Ukraine	Kyiv Center for Bone Marrow Transplantation	Kyiv
Ukraine	Institute of Blood Pathology and Transfusion Medicine	Lviv
Ukraine	Poltava M.V. Sklifosovskyi Regional Clinical-Hospital	Poltava
Ukraine	A. Novak Zakarpattia Regional Clinical Hospital	Uzhgorod
Ukraine	M.I. Pyrohov Vinnytsya Regional Clinical Hospital, Hematology Department	Vinnitsya
Ukraine	O.F. Herbachevskyi Regional Clinical Hospital, Hematology Center	Zhytomyr
United Kingdom	Kent and Canterbury Hospital	Canterbury	Kent
United Kingdom	Northwick Park Hospital	Harrow	Middlesex
United Kingdom	Raigmore Hospital	Inverness
United Kingdom	Guy's and St. Thomas' NHS Foundation Trust	London
United Kingdom	University College London, Cancer Centre	London
United Kingdom	Maidstone Hospital, Kent Oncology Centre	Maidstone	Kent
United Kingdom	Oxford University Hospitals NHS Trust, Churchill Hospital	Oxford
United Kingdom	The Royal Wolverhampton Hospitals NHS Trust, New Cross Hospital	Wolverhampton
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Maimonides Cancer Center	Brooklyn	New York
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Evanston KelIogg Cancer Center	Evanston	Illinois
United States	California Cancer Associates for Research & Excellence, Inc. (cCARE)	Fresno	California
United States	UF Health Shands Cancer Hospital	Gainesville	Florida
United States	Marin Cancer Care	Greenbrae	California
United States	Saint Francis Health System	Greenville	South Carolina
United States	Sutter Gould Medical Foundation	Modesto	California
United States	Weill Cornell Medical Center	New York	New York
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Spartanburg Regional Healthcare System	Spartanburg	South Carolina
United States	Santee Hematology Oncology	Sumter	South Carolina
United States	Innovative Clinical Research Institute	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (2)

Chari A, Stewart AK, Russell SD, Moreau P, Herrmann J, Banchs J, Hajek R, Groarke J, Lyon AR, Batty GN, Ro S, Huang M, Iskander KS, Lenihan D. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv. 2018 Jul 10;2(13):1633-1644. doi: 10.1182/bloodadvances.2017015545. Review. — View Citation

Facon T, Lee JH, Moreau P, Niesvizky R, Dimopoulos M, Hajek R, Pour L, Jurczyszyn A, Qiu L, Klippel Z, Zahlten-Kumeli A, Osman M, Paiva B, San-Miguel J. Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 2019 May 2;133(18):1953-1963. doi: 10.1182/blood-2018-09-874396. Epub 2019 Feb 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	Progression-free survival was defined as the time from randomization to the earlier of documented disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier methods. The duration of PFS was censored for participants with no baseline and/or post-baseline disease assessments, who started a new anti-cancer therapy before documentation of disease progression or death, death or disease progression after missed disease assessment of 100 consecutive days or longer, or who were alive without documentation of disease progression before the data cutoff date, including lost to follow-up prior to disease progression.; Participants were evaluated for disease response and progression according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC), determined centrally using a validated computer algorithm in a blinded manner.	From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
Secondary	Overall Survival (OS)	Overall survival (OS) was defined as the time from randomization to the date of death (whatever the cause). Participants who were alive or lost to follow-up as of the data analysis cut-off date were censored on the date the patient was last known to be alive.; Median overall survival was estimated using the Kaplan-Meier method.	From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively.
Secondary	Overall Response Rate	Disease response was evaluated according to the IMWG-URC using a validated computer algorithm. Overall response 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.	Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
Secondary	Complete Response Rate	Complete response rate was defined as the percentage of participants in each treatment group who achieved a sCR or CR per the IMWG-URC as their best response.; 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.	Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
Secondary	Percentage of Participants With = Grade 2 Peripheral Neuropathy	Neuropathy events were defined as Grade 2 or higher peripheral neuropathy as specified by peripheral neuropathy Standardised Medical Dictionary for Regulatory Activities (MedDRA) Query, narrow (scope) (SMQN) terms.; Peripheral neuropathy was assessed by neurologic exam and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: Grade 1: Asymptomatic; Grade 2: Moderate symptoms, limiting instrumental activities of daily living (ADL) Grade 3: Severe symptoms; limiting self-care ADL; Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death.	From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.
Secondary	European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores	The EORTC QLQ-C30 is a validated self-rating questionnaire including 30 items used to assess the overall quality of life in cancer patients.; It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).; The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with higher scores indicating better Global Health Status/QOL.	Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48
Secondary	Number of Participants With Adverse Events	Adverse events (AEs)were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where GRADE 1 = Mild; GRADE 2 = Moderate; GRADE 3 = Severe; GRADE 4 = Life-threatening; GRADE 5 = Fatal.; A serious adverse event is an adverse event that met 1 or more of the following criteria: Death; Life-threatening; Required inpatient hospitalization or prolongation of an existing hospitalization; Resulted in persistent or significant disability/incapacity; Congenital anomaly/birth defect; Important medical event that jeopardized the participant and may have required medical or surgical intervention to prevent 1 of the outcomes listed above.; Treatment-related adverse events are adverse events considered related to at least 1 investigational product by the investigator, including those with unknown relationship.	From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.

External Links

•   AmgenTrials clinical trials website