AzTrials
AzTrials

Multiple MyelomaPhase 3CLARIONNCT01818752

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

A Phase 3 study testing Carfilzomib, Bortezomib and Melphalan in people with Multiple Myeloma, run by Amgen at 213 sites in 30 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). 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, Bortezomib and Melphalan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
955 participants
Where
213 sitesin 30 countries
Study dates
8 Jul 2013to 4 Nov 2016
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

  • Newly diagnosed symptomatic multiple myeloma (per International Myeloma Working Group [IMWG] diagnostic criteria)
  • Transplant ineligibility
  • 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)
  • No prior treatment for multiple myeloma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Who cannot join

  • Multiple myeloma of IgM (immunoglobulin M) subtype
  • Glucocorticoid therapy within 14 days prior to randomization that equals or exceeds a cumulative dose of 160 mg of dexamethasone
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
  • Waldenström macroglobulinemia (WM)
  • Known amyloidosis

Trial locations and contacts

213 sites in 30 countries.

213 sites in 30 countries

China16 sites

  • 307 Hospital of PLA

    Beijing

  • Beijing Chao Yang Hospital, Capital Medical University

    Beijing

  • Peking Union Medical College Hospital

    Beijing

  • Peking University Third Hospital

    Beijing

  • The First Hospital of Jilin University

    Changchun, Jilin

  • Fujian Medical University Union Hospital

    Fuzhou, Fujian

  • Guangdong General Hospital

    Guangzhou, Guangdong

  • Guangzhou First People's Hospital

    Guangzhou, Guangdong

  • The First Affiliated Hospital of College of Medicine, Zhejiang University - Dr. Jie Jin

    Hangzhou, Zhejiang

  • The First Affiliated Hospital of College of Medicine, Zhejiang University

    Hangzhou, Zhejiang

  • Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine

    Shanghai

  • Shanghai Changzheng Hospital

    Shanghai

  • The First Affiliated Hospital of Soochow University

    Suzhou, Jiangsu

  • Institute on Hematology & Blood Diseases Hospital Chinese Academy of Medical Scicnces & Peking Union Medical University

    Tianjin

  • Tianjin Medical University Cancer Institute and Hospital

    Tianjin

  • The First Affiliated Hospital of the Fourth Military Medical University of PLA

    Xi’an, Shanxi

Other trials in China

France16 sites

  • CHU de Caen, Côte de Nacre

    Caen, 14033

  • CHU Estaing

    Clermont-Ferrand, 63000

  • UHC Dijon, Children's Hospital

    Dijon

  • CHRU Lille Hôpital Claude Huriez

    Lille, 59037

  • CHRU Hopital Huriez, Departement of Hematology

    Lille

  • Paoli Calmettes Institute, Department ofHematology 2

    Marseille

  • Nantes University Hospital Center

    Nantes, 44093

  • Centre Hospitalier Regional Universitaire de Nimes, Groupe Hospitalo-Universitaire Caremeau

    Nîmes

  • Hopital Saini Louis, Service d'immuno-Hematologie

    Paris

  • Hopital Saint Antoine

    Paris

  • Hospital Necker

    Paris

  • South Lyon Hospital Center

    Pierre-Bénite, 69310

  • Centre Hospitalier Lyon Sud, Service d'hématologie Clinique

    Pierre-Bénite, 69495

  • Hopital Pontchaillou

    Rennes

  • Hospital Purpan

    Toulouse

  • CHU de Tours Hopital Bretonneau

    Tours

Other trials in France

Japan16 sites

  • Kyushu University Hospital

    Fukuoka, Fukuoka

  • The Cancer Institute Hospital of Japanese Foundation For Cancer Research

    Koto, Tokyo

  • University Hospital, Kyoto Prefectural University of Medicine

    Kyoto

  • Gunma University Hospital

    Maebashi, Gunma

  • National Hospitalization Organization Kyushu Cancer Center

    Minamiku, Fukuoka

  • Nagoya City University Hospital

    Nagoya, Aichi-ken

  • Ogaki Municipal Hospital

    Ōgaki, Gifu

  • National Hospital Organization Okayama Medical Center

    Okayama, Okayama-ken

  • Sapporo Medical University Hospital

    Sapporo, Hokkaido

  • National Center for Global Health and Medicine

    Shinjuku, Tokyo

  • Osaka University Hospital

    Suita, Osaka

  • National Hospital Organization Disaster Medical Center

    Tachikawa, Tokyo

  • Tokushima Prefectural Central Hospital

    Tokushima

  • Japanese Red Cross Medical Center

    Tokyo, Shibuya-ku

  • Toyohashi Municipal Hospital

    Toyohashi, Aichi-ken

  • Tochigi Cancer Center

    Utsunomiya, Tochigi

Other trials in Japan

United States14 sites

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Maimonides Cancer Center

    Brooklyn, New York

  • Gabrail Cancer Center Research

    Canton, Ohio, 44718

  • Evanston KelIogg Cancer Center

    Evanston, Illinois

  • California Cancer Associates for Research & Excellence, Inc. (cCARE)

    Fresno, California, 93720

  • UF Health Shands Cancer Hospital

    Gainesville, Florida

  • Marin Cancer Care

    Greenbrae, California, 94904

  • Saint Francis Health System

    Greenville, South Carolina, 29601

  • Sutter Gould Medical Foundation

    Modesto, California, 95357

  • Weill Cornell Medical Center

    New York, New York, 10021

  • Seattle Cancer Care Alliance

    Seattle, Washington

  • Spartanburg Regional Healthcare System

    Spartanburg, South Carolina, 29303

  • Santee Hematology Oncology

    Sumter, South Carolina, 29150

  • Innovative Clinical Research Institute

    Whittier, California, 90603

Other trials in United States

South Korea12 sites

  • Pusan National University Hospital

    Busan, 602-739

  • Inje University Busan Paik Hospital

    Busan, 614-735

  • Kyungpook National University Hospital

    Daegu, 700-721

  • National Cancer Center

    Goyang-si, Gyeonggi-do

  • Chonnam National University Hwasun Hospital

    Hwasun-gun, Jeollanam-do, 519-763

  • Gachon University Gil Medical Center

    Incheon, 405-760

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do, 463-707

  • Seoul National University Hospital

    Seoul, 110-774

  • Severance Hospital, Yonsei University Health System

    Seoul, 120-752

  • Samsung Medical Center

    Seoul, 135-710

  • The Catholic University of Korea, Seoul St. Mary's Hospital

    Seoul, 137-701

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

Australia10 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Eastern Health - Box Hill Hospital

    Box Hill, Victoria, 3128

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • St. Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • St. Vincent's Hospital Melbourne

    Fitzroy, Victoria

  • The Alfred Hospital

    Melbourne, Victoria, 3004

  • Royal North Shore Hospital, Haematology Department

    New South Wales

  • Central Coast Local Health District

    North Gosford, New South Wales, 2250

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

  • Border Medical Oncology

    Wodonga, Victoria, 3690

Other trials in Australia

Ukraine10 sites

  • Cherkasy Regional Oncology Center

    Cherkasy, 18009

  • Dnipropetrovsk City Multispecialty Clinical Hospital #4, Hematology Centre

    Dnipropetrovsk, 49102

  • Kharkiv Regional Clinical Oncology Center, Department of Hematology

    Kharkiv, 61070

  • Khmelnytskyi Regional Hospital, Hematology Department

    Khmelnytskyi, 29000

  • Kyiv Center for Bone Marrow Transplantation

    Kyiv, 03 115

  • Institute of Blood Pathology and Transfusion Medicine

    Lviv, 79044

  • Poltava M.V. Sklifosovskyi Regional Clinical-Hospital

    Poltava

  • A. Novak Zakarpattia Regional Clinical Hospital

    Uzhhorod

  • M.I. Pyrohov Vinnytsya Regional Clinical Hospital, Hematology Department

    Vinnitsya, 21018

  • O.F. Herbachevskyi Regional Clinical Hospital, Hematology Center

    Zhytomyr, 10002

Other trials in Ukraine

Russia9 sites

  • Arkhangelsk Regional Clinical Hospital, Department of internal diseases #2

    Arkhangelsk

  • State Medical Institution: First Republican Clinical Hospital under the Ministry of Healthcare of the Republic of Udmurtia

    Izhevsk, 426039

  • 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, 115478

  • City Clinical Hospital N.A.S.P. Botkin, Department of Bone Marrow Transplantation and Intensive Chemotherapy for Patients with Myeloproliferative Disorders

    Moscow, 125284

  • State Medical Institution: Republican Hospital n a.V.A. Baranov, Department of Hematology

    Petrozavodsk, Republic of Karelia, 185019

  • Federal State Institution: Russian Research Institute of Hematology and Blood Transfusion under the Federal Agency for High-Tech Medical Care

    Saint Petersburg, 191024

  • City Clinical Hospital #31, Department of Bone Marrow Transplantation and Intensive Chemotherapy for Patients with Myeloproliferative Disorders

    Saint Petersburg, 197110

  • State Higher Educational Institution St. Petersburg Pavlov State Medical University

    Saint Petersburg

  • The Federal State Budget Institute The Nikiforov Russian Center of Emergency and Radiation Medicine the Ministry of Russian

    Saint Petersburg

Other trials in Russia

Germany8 sites

  • University Hospital Cologne

    Cologne, North Rhine-Westphalia, 50937

  • Group Practice for Hematology and Oncology

    Dresden, 1307

  • Freiburg University Medical Center

    Freiburg im Breisgau, Baden-Wurttemberg

  • Saarland University Hospital

    Homburg / Saar, Saarland

  • Stiftungsklinikum Mittelrhein GmbH, Clinic of Internal Medicine

    Koblenz, 56068

  • Johannes Gutenberg-University Mainz, Medical Clinic and Policlinic III

    Mainz, Rhineland-Palatinate

  • Ludwig Maximilians University Hospital - Medical Clinic III

    Munich, Bavaria

  • Ulm University Hospital, Center for Internal Medicine, Clinic of Internal Medicine III

    Ulm, Baden-Wurttemberg

Other trials in Germany

Italy8 sites

  • Ospedali Riuniti di Ancona Umberto I, G.M. Lancisi, G. Salesi

    Ancona

  • UO Clinica Ematologica, IRCCS A.O.U. San Martino

    Genova, GE

  • Maggiore della Carita Hospital of Novara

    Novara

  • A.O.U. San Luigi Gonzaga

    Orbassano, TO

  • Local NHS of Piacenza Hospital Guglielmo da Saliceto Department Oncology-Hematology, Unit of Hema

    Piacenza

  • Ospedale S. Eugenio

    Roma

  • Policlinico Universitario "Umberto I"

    Rome

  • AO Città della Salute e della Scienza di Torino, Division of Hematology

    Torino, 10126

Other trials in Italy

Poland8 sites

  • Independent Public Healthcare Facility Municipal Hospital Group, Department of Hematology

    Chorzów, Silesian Voivodeship, 41-500

  • Andrzej Mielecki Independent Public Clinical Hospital of Medical University of Silesia in Katowice

    Katowice, 40-032

  • Independent Public Healthcare Facility University Hospital

    Krakow

  • Nicolaus Copernicus Memorial Provincial Specialist Hospital

    Lodz

  • Independent Public Teaching Hospital No.1 in Lublin, Dept. of Hematology-Oncology

    Lublin

  • Independent Public Healthcare Facility of the Ministry of Internal Affairs & Warminsko-Mazurskie Oncology Centre in Olsztyn

    Olsztyn, OIsztyn

  • Nicolaus Copernicus Municipal Specialist Hospital, Department of Hematology

    Torun, 87-100

  • Maria Sklodowska-Curie Institute of Oncology

    Warsaw, 02-781

Other trials in Poland

Spain8 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barselona, 8916

  • Hospital Clinic i Provincial Barcelona

    Barcelona

  • Hospital Universitario 12 De Octubre

    Madrid, 28041

  • University Hospital of Navarra

    Pamplona, Navarre

  • Hospital Universitario, Salamanca

    Salamanca, 37007

  • Hospital Virgen del Rocio University

    Seville, 41013

  • Universitari i Politècnic la Fe de Valencia Consulta Externa de Hematología

    Valencia, 46026

  • Hospital Quiron Zaragoza

    Zaragoza

Other trials in Spain

United Kingdom8 sites

  • Kent and Canterbury Hospital

    Canterbury, Kent, CTI 3NG

  • Northwick Park Hospital

    Harrow, Middlesex

  • Raigmore Hospital

    Inverness, IV2 3UJ

  • University College London, Cancer Centre

    London, NW1 2PG

  • Guy's and St. Thomas' NHS Foundation Trust

    London, SE1 9RT

  • Maidstone Hospital, Kent Oncology Centre

    Maidstone, Kent, ME16 9QQ

  • Oxford University Hospitals NHS Trust, Churchill Hospital

    Oxford, OX3 7LE

  • The Royal Wolverhampton Hospitals NHS Trust, New Cross Hospital

    Wolverhampton, WV10 0QP

Other trials in United Kingdom

Czechia7 sites

  • University Hospital Brno, Department of Internal Hematology and Oncology

    Brno, 625 00

  • University Hospital Brno, Hospital Pharmacy - Department of Dilution of Cytostasis

    Brno, 625 00

  • University Hospital Hradec Kralove

    Hradec Králové, 500 05

  • University Hospital Olomouc, 3rd Clinic of Internal Medicine, Nephrology, Rheumatology and Endocrinology

    Olomouc, 775 20

  • University Hospital Ostrava, Clinic of Hematooncology of UHO and MFUO

    Ostrava, 708 52

  • University Hospital Kralovske Vinohrady - Internal Hematology Clinic

    Prague, 10034

  • General University Hospital Prague, 1st Department of Medicine - Department of Hematology

    Prague, 128 08

Other trials in Czechia

Hungary7 sites

  • St. Istvan and St. Laszlo Hospital of Budapest, Department of Haematology and Stem-cell Transplant

    Budapest, 1097

  • National Institute of Oncology, Department of Oncology, Internal Medicine "A" and Hematology

    Budapest, 1122

  • University of Debrecen, Medical and Health Science Center, Institute for Medicine, Chair of Hematology

    Debrecen, 4032

  • Bekes County Pandy Kalman Hospital 1st Department of Internal Medicine, Hematology

    Gyula, 5700

  • Kaposi Mor County Teaching Hospital, 2nd Department of Internal Medicine, Hematology

    Kaposvár, 7400

  • Bacs-Kiskun County Teaching Hospital, II. Department of Internal Medicine

    Kecskemét, 6000

  • Medical Center of the University of Pecs, 1st Clinic for Internal Medicine

    Pécs, 7624

Other trials in Hungary

Romania7 sites

  • Brasov County Emergency Clinical Hospital, Hematology Department

    Brasov, 500326

  • Fundeni Clinical Institute, Hematology Department

    Bucharest, 022 328

  • Coltea Clinical Hospital, Hematology Department

    Bucharest, 030 171

  • Bucharest Emergency University Hospital, Hematology Department

    Bucharest, 50098

  • "Prof. Dr. Ion Chiricuta" Institut of Oncology, Hematology Department

    Cluj-Napoca, Cluj, 400124

  • Iasi Regional Institute for Oncology, Medical Hematology Department

    Iași, Iaşi, 700483

  • Targu-Mures County Emergency Clinical Hospital, Clinic of Hematology and Bone Marrow Transplantation

    Târgu Mureş, 540042

Other trials in Romania

Taiwan6 sites

  • Changhua Christian Hospital

    Changhua

  • Kuohsiung Chang Gung Memorial Hospital

    Kaohsiung City

  • China Medical University Hospital

    Taichung, 40447

  • National Taiwan University Hospital

    Taipei, 100

  • Taipei Veterans General Hospital

    Taipei

  • Chang-Gung Memorial Hospital, Linkou

    Tapei

Other trials in Taiwan

Bulgaria5 sites

  • University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Hematology Clinic

    Plovdiv, 4002

  • University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Oncology and Hematology Clinic

    Plovdiv, 4002

  • Military Medical Academy - Multiprofile Hospital for Active Treatment, Sofia, Hematology and Oncology Clinic

    Sofia, 1606

  • Specialized Hospital for Active Treatment of Hematological Diseases, Sofia, Hematology Clinic

    Sofia, 1756

  • Multiprofile Hospital for Active Treatment "Sveta Marina", Varna

    Varna, 9010

Other trials in Bulgaria

Singapore5 sites

  • National University Hospital

    Singapore, 119228

  • Singapore General Hospital

    Singapore, 169608

  • Singapore Oncology Consultants, Gleneagles Hospital

    Singapore, 258500

  • OncoCare Cancer Center

    Singapore

  • Singapore General Hospital

    Singapore

Other trials in Singapore

Belgium4 sites

  • ZNA, Stuivenberg

    Antwerp, Antwerpen, 2060

  • Saint Joseph Clinic Arlon, Department of Hematology

    Arlon, Luxembourg, 6700

  • CHR de La Citadelle (ENG: Citadelle Regional Hospital Center)

    Liège, 4000

  • CHU Mont-Godinne

    Yvoir, 5530

Other trials in Belgium

Israel4 sites

  • Soroka University Medical Center

    Beersheba, P.O.B 151

  • Rambam Medical Center, Department of Hematology

    Haifa, 31096

  • Ein Kerem Hospital, Department of Hematology

    Jerusalem, 91120

  • The Chaim Sheba Medical Center

    Tel HaShomer

Other trials in Israel

Mexico4 sites

  • Fundacion Centro Oncologieo de Integracion Regional - COIR

    Mendoza

  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

    Mexico City

  • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"

    Monterrey, Nuevo León

  • Consultorio Privado del Dr. Guillermo Jose Ruiz y Arguelles

    Puebla City

Other trials in Mexico

Netherlands4 sites

  • Vrije Universiteit Medisch Centrum (VUMC), Department of Hematology

    Amsterdam

  • St. Antonius Ziekenhuis, Department of Hematology

    Nieuwegein

  • Erasmus Medical Center

    Rotterdam

  • Isala Clinics in Zwolle, Department of Oncology

    Zwolle

Other trials in Netherlands

New Zealand4 sites

  • North Shore Hospital

    Auckland, 0622

  • Auckland City Hospital

    Auckland, 1023

  • Canterbury Health Laboratories

    Christchurch, 8011

  • Wellington Hospital

    Wellington, 6021

Other trials in New Zealand

Austria3 sites

  • Medical University of Innsbruck, University Clinic for Internal Medicine V

    Innsbruck, 6020

  • Elisabeth Linz Hospital

    Linz, 4020

  • Vienna Wilhelminen Hospital

    Vienna, 1160

Other trials in Austria

Turkey (Türkiye)3 sites

  • Ankara University Medical Faculty, Cebeci Research and Application Hospital, Hematology Department

    Ankara, Cebeci, 06590

  • Marmara University Pendik Training and Research Hospital

    Istanbul, Pendik

  • Ege University Medical Faculty

    Izmir, Bornova

Other trials in Turkey (Türkiye)

Argentina2 sites

  • Centro de educacion medica c investigacioncs clinicas "Norberto Quimo' (CEMIC)

    Buenos Aires

  • Sanatorio Britanico S.A.

    Santa Fe

Other trials in Argentina

Greece2 sites

  • Evangelismos Hospital

    Athens, Attica, 10676

  • University of Athens, Alexandra Hospital

    Athens, 11528

Other trials in Greece

Switzerland2 sites

  • University Hospital Center Vaudois

    Lausanne

  • County Hospital Saint Gallen

    Sankt Gallen

Other trials in Switzerland

Canada1 site

  • CSSS-Champlain-Charles LeMoyne

    Greenfield Park, Quebec

Other trials in Canada

About this study

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

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).

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 Krypolis®

    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.

  • BortezomibDrug

    Also called Velcade®

    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.

  • MelphalanDrug

    Melphalan 9 mg/m² was taken orally on days 1 to 4 of all cycles.

  • PrednisoneDrug

    Prednisone 60 mg/m² was taken orally on days 1 to 4 of all cycles.

Study groups in NCT01818752
Study groupRoleWhat they receive
Carfilzomib, Melphalan, PrednisoneExperimentalParticipants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Receives: Drug: Carfilzomib; Drug: Melphalan; Drug: Prednisone
Bortezomib, Melphalan, PrednisoneActive comparatorParticipants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
Receives: Drug: Bortezomib; Drug: Melphalan; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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 outcomes (6)

  1. 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.

    Measured: 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.

  2. 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.

    Measured: 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.

  3. 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.

    Measured: 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.

  4. 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.

    Measured: 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.

  5. 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.

    Measured: Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48

  6. 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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2013 (estimated)
  2. Study start8 Jul 2013
  3. Primary completion15 Jul 2016
  4. Study completion4 Nov 2016

Resources

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
955 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01818752
Sponsor's protocol ID
2012-005
Other IDs
2012-005283-97, 20130397
Acronym
CLARION
Status last verified
Aug 2019
First submitted
12 Feb 2013
Last updated
26 Aug 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29991494

  • 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.

    PubMed 30819926

  • Rosenthal A, Luthi J, Belohlavek M, Kortum KM, Mookadam F, Mayo A, Fonseca R, Bergsagel PL, Reeder CB, Mikhael JR, Stewart AK. Carfilzomib and the cardiorenal system in myeloma: an endothelial effect? Blood Cancer J. 2016 Jan 15;6(1):e384. doi: 10.1038/bcj.2015.112.

    PubMed 26771810

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Carfilzomib, Bortezomib and Melphalan in people with Multiple Myeloma, run by Amgen at 213 sites in 30 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 8 inclusion and 6 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 26 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 213 sites in China, France, Japan, United States, South Korea and 25 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 1 Aug 2017). 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 (PFS) (time frame: 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.). 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 NCT01818752, which also lists 3 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 26 Aug 2019.

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