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Multiple MyelomaPhase 3ENDEAVORNCT01568866

Phase 3 Study With Carfilzomib and Dexamethasone Versus Bortezomib and Dexamethasone for Relapsed Multiple Myeloma Patients

A Phase 3 study testing Carfilzomib, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Amgen at 241 sites in 27 countries.

Completed

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

Official record
Search all trials

Trial summary

The primary objective of this study was to compare progression-free survival in patients with multiple myeloma who relapsed after 1 to 3 prior therapies treated with carfilzomib plus dexamethasone or bortezomib plus dexamethasone. 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 Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
929 participants
Where
241 sitesin 27 countries
Study dates
20 Jun 2012to 5 Feb 2018
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

  • Multiple myeloma with relapsing or progressing disease at study entry.
  • Patients must have evaluable multiple myeloma with, at least one of the following (assessed within 21 days prior to randomization):
  • Serum M-protein ≥ 0.5 g/dL, or
  • Urine M-protein ≥ 200 mg/24 hour, or
  • In patients without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa/lamda ratio, or
  • For immunoglobulin (Ig) A patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL).
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  • Patients must have documented at least partial response (PR) to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment.
  • Received 1, but no more than 3 prior treatment regimens or lines of therapy for multiple myeloma. (Induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as one line of therapy).
  • Prior therapy with Velcade is allowed as long as the patient had at least a PR to prior Velcade therapy, was not removed from Velcade therapy due to toxicity, and will have at least a 6 month Velcade treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month Velcade treatment-free interval).
  • Prior therapy with carfilzomib is allowed as long as the patient had at least a PR to prior carfilzomib therapy, was not removed from carfilzomib therapy due to toxicity, and had at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month carfilzomib treatment-free interval). The exception to this is patients randomized or previously randomized in any other Onyx-Sponsored Phase 3 trial.
  • Males and females ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
  • Adequate hepatic function within 21 days prior to randomization, with bilirubin < 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN.
  • Left ventricular ejection fraction (LVEF) ≥ 40%.
  • Absolute neutrophil count (ANC) ≥ 1000/mm³ within 21 days prior to randomization. Screening ANC should be independent of growth factor support for ≥ 1 week.
  • Hemoglobin ≥ 8.0 g/dL within 21 days prior to randomization. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed, however 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%) within 21 days prior to randomization. Patients 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 ≥ 15 mL/min within 21 days prior to randomization. Calculation should be based on standard formula such as the Cockcroft and Gault:
  • [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female.
  • Written informed consent in accordance with federal, local, and institutional guidelines.
  • Female patients of child-bearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to randomization and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP.

Who cannot join

  • Multiple Myeloma of IgM subtype.
  • Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization.
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
  • Plasma cell leukemia or circulating plasma cells ≥ 2 × 10^9/L.
  • Waldenstrom's Macroglobulinemia.
  • Patients with known amyloidosis.
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  • Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to randomization.
  • Patients randomized or previously randomized in any other Onyx-Sponsored Phase 3 trial.
  • Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow).
  • Immunotherapy within 21 days prior to randomization.
  • Major surgery (excluding kyphoplasty) within 28 days prior to randomization.
  • Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior to randomization.
  • Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to randomization.
  • Known human immunodeficiency (HIV) seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).
  • Patients with known cirrhosis.
  • Second malignancy within the past 3 years except:
  • adequately treated basal cell or squamous cell skin cancer
  • carcinoma in situ of the cervix
  • prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
  • breast carcinoma in situ with full surgical resection
  • treated medullary or papillary thyroid cancer
  • Patients with myelodysplastic syndrome.
  • Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days prior to randomization.
  • Female patients who are pregnant or lactating.
  • Known history of allergy to Captisol(a cyclodextrin derivative used to solubilize carfilzomib).
  • Patients with hypersensitivity to carfilzomib, Velcade, boron, or mannitol.
  • Patients with contraindication to dexamethasone.
  • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
  • Ongoing graft-vs-host disease.
  • Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization.

Trial locations and contacts

241 sites in 27 countries.

241 sites in 27 countries

United States27 sites

  • University of Michigan

    Ann Arbor, Michigan

  • Winship Cancer Institute

    Atlanta, Georgia

  • Center for Cancer and Blood Disorders

    Bethesda, Maryland

  • Providence St. Joseph Medical Center

    Burbank, California

  • Gabrail Cancer Center

    Canton, Ohio

  • The Christ Hospital

    Cincinnati, Ohio

  • Colorado Blood Cancer Institute

    Denver, Colorado

  • Hematology/Oncology Associates of SC

    Greenville, South Carolina

  • Hackensack University Medical Ctr

    Hackensack, New Jersey

  • MD Anderson

    Houston, Texas

  • The Methodist Cancer Center

    Houston, Texas

  • Hematology Oncology of Indiana, PC

    Indianapolis, Indiana

  • University of Kansas

    Kansas City, Missouri

  • UCSD Moore Cancer Center

    La Jolla, California

  • UCLA Medical Center

    Los Angeles, California

  • MAB Oncology/Hematology

    Melbourne, Florida

  • Vanderbilt Ingram Cancer Center

    Nashville, Tennessee

  • Clinical Research Alliance Inc.

    New York, New York

  • Weill Cornell Medical College

    New York, New York

  • Western Pennsylvania Hospital

    Pittsburgh, Pennsylvania

  • Associates in Oncology/Hematology PC

    Rockville, Maryland

  • University of Utah School of Medicine

    Salt Lake City, Utah

  • Central Coast Medical Oncology Group

    Santa Maria, California

  • Scott & White Memorial Hospital

    Temple, Texas

  • Montefiore Medical Center

    The Bronx, New York

  • Palm Beach Cancer Institute

    West Palm Beach, Florida

  • Wake Forest University Health Sciences, Section on Hematology and Oncology

    Winston-Salem, North Carolina

Other trials in United States

Japan24 sites

  • National Cancer Center Hospital

    Chuo-ku, Tokyo

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, Fukuoka

  • Kyushu University Hospital

    Fukuoka

  • Tokai University Hospital

    Isehara, Kanagawa

  • Saitama Medical Center

    Kawagoe, Saitama

  • Kobe City Medical Center General Hospital

    Kobe, Hyōgo

  • The Cancer Institute Hospital Of Japanese Foundation For Cancer Research

    Koto-ku, Tokyo

  • Social Insurance Kyoto Hospital of All Japan Federation of Social Insurance Associations

    Kyoto

  • University Hospital, Kyoto Prefectural University of Medicine

    Kyoto

  • Gunma University Hospital

    Maebashi, Gunma

  • Nagoya City University Hospital

    Nagoya, Aichi-ken

  • Niigata Cancer Center Hospital

    Niigata, Niigata

  • Ogaki Municipal Hospital

    Ōgaki, Gifu

  • National Hospital Organization Okayama Medical Center

    Okayama

  • Sapporo Medical University Hospital

    Sapporo, Hokkaido

  • National Hospital Organization Nishigunma National Hospital

    Shibukawa, Gunma

  • Toranornon Hospital

    Shinagawa, Tokyo

  • Tokyo Medical University Hospital

    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

  • Toyohashi Municipal Hospital

    Toyohashi, Aichi-ken

  • Tochigi Cancer Center

    Utsunomiya, Tochigi

Other trials in Japan

Australia21 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia

  • Box Hill Hospital

    Box Hill, Victoria

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales

  • Monash Medical Centre

    Clayton, Victoria

  • St. Vincent's Public Hospital Sydney

    Darlinghurst, New South Wales

  • Saint Vincent's Hospital

    East Melbourne, Victoria

  • Western Hospital

    Footscray, Victoria

  • Fremantle Hospital

    Fremantle, Western Australia

  • Royal Brisbane and Women's Hospital

    Herston, Queensland

  • Saint George Hospital

    Kogarah, New South Wales

  • Liverpool Hospital

    Liverpool, New South Wales

  • The Alfred Hospital

    Melbourne, Victoria

  • Royal Perth Hospital

    Perth, Western Australia

  • Royal North Shore Hospital

    Saint Leonards, New South Wales

  • Haematology & Oncology Clinics of Australia

    South Brisbane, Queensland

  • Haematology and Oncology Clinics of Australia at Chermside

    South Brisbane, Queensland

  • Haematology and Oncology Clinics of Australia at Wesley

    South Brisbane, Queensland

  • Sunshine Hospital

    St Albans, Victoria

  • Calvary Mater Newcastle

    Waratah, New South Wales

  • Westmead Hospital

    Westmead, New South Wales

  • The Queen Elizabeth Hospital

    Woodville, South Australia

Other trials in Australia

Germany15 sites

  • Universitätsklinikum Aachen

    Aachen, North Rhine-Westphalia

  • Klinikum Chemnitz gGmbH

    Chemnitz, Saxony

  • Universitätsklinikum Carl Gustav Carus, Med. Klinik und Poliklinik I

    Dresden, Saxony

  • Universitatsklinikum Freiburg

    Freiburg im Breisgau

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg

  • Medizinische Hochschule Hannover

    Hanover, Lower Saxony

  • Universitätsklinik Heidelberg

    Heidelberg, Baden-Wurttemberg

  • Universitätsklinikum des Saarlandes

    Homburg / Saar, Saarland

  • Universitätsklinikum Jena

    Jena, Thuringia

  • Universitätsklinikum Leipzig

    Leipzig, Saxony

  • Universitätsmedizin der Johannes Gutenberg Universität

    Mainz, Rhineland-Palatinate

  • Universitätsklinikum Münster

    Münster, North Rhine-Westphalia

  • Universitätsklinikum Tübingen

    Tübingen, Baden-Wurttemberg

  • Universitätsklinikum Ulm

    Ulm, Baden-Wurttemberg

  • Medizinische Klinik der Universität Würzburg

    Würzburg, Bavaria

Other trials in Germany

Italy14 sites

  • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

    Ancona

  • Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi

    Bologna

  • Azienda Ospedaliera Spedali Civili di Brescia

    Brescia

  • IRCCS Azienda Ospedaliera Universitaria San Martino

    Genova

  • Azienda Ospedaliera Universitaria Maggiore della Carità

    Novara

  • Azienda Ospedaliero-Univesitaria San Luigi Gonzaga

    Orbassano, Torino

  • Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto

    Piacenza

  • Azienda Ospedaliera Pisana Ospedale Santa Chiara

    Pisa

  • IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture

    Rionero in Vulture, Potenza

  • Aienda Policknico Umberto I di Roma

    Roma

  • Azienda Policknico Umberto l di Roma

    Roma

  • Università Tor Vergata Ospedale Sant Eugenio

    Roma

  • Azienda Ospedaliera Universitaria Senese - Policlinico S. Maria alle Scotte

    Siena

  • Azienda Ospedaliera Città della Salute e della Scienza di Torino

    Torino

Other trials in Italy

France12 sites

  • Centre Hospitalier de la Cote Basque

    Bayonne, Aquitaine

  • Centre Hospitalier Universitaire Brest

    Brest, Brittany Region

  • Centre Hospitalier de Versailles

    Le Chesnay, Île-de-France Region

  • Hôpital Claude Huriez

    Lille, Hauts-de-France

  • Institut Paoli Calmettes

    Marseille, Provence-Alpes-Côte d'Azur Region

  • Hopital Hotel-Dieu - Service d'Hematologie

    Nantes, Cedex 1

  • Hôpital Hôtel-Dieu

    Nantes, Pays de la Loire Region

  • Hôpital Saint Louis

    Paris, Île-de-France Region

  • Hôpital Saint-Antoine

    Paris, Île-de-France Region

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, Auvergne-Rhône-Alpes

  • Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou

    Rennes, Brittany Region

  • Centre Henri-Becquerel

    Rouen, Haute-normandie

Other trials in France

Ukraine12 sites

  • Cherkassy Regional Oncology Center

    Cherkassy

  • City Hematology Center

    Dnipro, Dnipropretrovsk

  • MI "Dnipropetrovsk City Multifield Clinical Hospital #4" of Dnipropetrovsk Regional Council", City Hematology Center

    Dnipropetrovsk

  • Institute of Urgent and Reparative Surgury of Ukraine Academy of Medical Sciences

    Donetsk

  • Municipal Institution of Health Protection "Clinical Hospital #8"

    Kharkiv, Kharkiv Oblast

  • Khmelnytsky Regional Clinical Hospital

    Khmelnytsky

  • Khmelnytsky Regional Hospital, Department of Hematology

    Khmelnytsky

  • National Institute of Cancer, Oncohematology Department

    Kiev

  • Kyiv Bone Marrow Transplantation Center

    Kyiv

  • Lviv Regional Oncology Dispensary

    Lviv

  • Lviv State Oncology Regional Treatment-Prophylactic Center, Department of Chemotherapy

    Lviv

  • Regional Clinical Hospital

    Mykolayiv

Other trials in Ukraine

Spain10 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona

  • Hospital Clinic I Provincial de Barcelona

    Barcelona

  • Institut Universitari Dexeus

    Barcelona

  • Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario La Princesa

    Madrid

  • Hospital Son Llàtzer

    Palma de Mallorca, Balearic Islands

  • Hospital Clínico Universitario de Salamanca

    Salamanca

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Universitari i Politecnic La Fé de Valencia

    Valencia

Other trials in Spain

Brazil9 sites

  • Hemocentro Campinas-Unicamp

    Campinas, São Paulo

  • Liga Norte Riograndense Contra o Câncer

    Natal, Rio Grande do Norte

  • Clínica de Oncologia de Porto Alegre

    Porto Alegre, Rio Grande do Sul

  • Hospital de Clínicas de Porto Alegre

    Porto Alegre, Rio Grande do Sul

  • Hospital São Lucas da PUCRS

    Porto Alegre, Rio Grande do Sul

  • Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro

    Rio de Janeiro

  • Instituto Centros Oncológicos Integrados de Educação e Pesquisa

    Rio de Janeiro

  • Instituto Nacional do Câncer-INCA

    Rio de Janeiro

  • Irmandade da Santa Casa de Misericórdia de São Paulo

    São Paulo

Other trials in Brazil

Russia9 sites

  • Republican Clinical Hospital #1

    Izhevsk

  • City Clinical Hospital n.a. S. P. Botkin

    Moscow

  • Non-state Healthcare Institution "N.A. Semashko Central Clinical Hospital #2 of JSC "Russian Railway

    Moscow

  • Ryazan Regional Clinical Hospital

    Ryazan

  • Clinical Hospital Number 31

    Saint Petersburg

  • Federal Almazov Medical Research Centre

    Saint Petersburg

  • FGU Russian Scientific Research Institute of Hematology and Transfusiology

    Saint Petersburg

  • First Saint Petersburg I.P. Pavlov State Medical University

    Saint Petersburg

  • GUZ Samara Regional Clinical Hospital n.a. M.I. Kalinin

    Samara

Other trials in Russia

South Korea9 sites

  • Kyungpook National University Hospital

    Daegu

  • Gachon University Gil Medical Center

    Incheon, Gyeonggi-do

  • Pusan National University Hospital

    Pusan, Gyeongsangnam-do

  • Seoul National University Bundang Hospital

    Seongnam-si, Gyeonggi-do

  • Asan Medical Center

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Seoul Saint Mary's Hospital

    Seoul

  • Severance Hospital, Yonsei University Health System

    Seoul

Other trials in South Korea

United Kingdom9 sites

  • Royal Free Hospital

    London, England

  • University College Hospital

    London, England

  • Manchester Royal Infirmary

    Manchester, England

  • Nottingham University Hospitals NHS Trust

    Nottingham, England

  • Churchill Hospital

    Oxford, England

  • Derriford Hospital

    Plymouth, England

  • Royal Hallamshire Hospital

    Sheffield, England

  • Royal Marsden Hospital

    Surrey, England

  • Royal Wolverhampton Hospitals Trust

    Wolverhampton, England

Other trials in United Kingdom

Canada8 sites

  • University of Alberta Hospital

    Edmonton, Alberta

  • Queen Elizabeth II Health Science Centre

    Halifax, Nova Scotia

  • British Columbia Cancer Agency

    Kelowna, British Columbia

  • London Health Sciences Centre

    London, Ontario

  • Hopital Maisonneuve-Rosemont

    Montreal, Quebec

  • The Ottawa Hospital Regional Cancer Centre

    Ottawa, Ontario

  • Saint John Regional Hospital

    Saint John, New Brunswick

  • Windsor Regional Hospital

    Windsor, Ontario

Other trials in Canada

Hungary7 sites

  • Egyesített Szent István és Szent László Kórház-Rendelointézet

    Budapest

  • Debreceni Egyetem Klinikai Központ

    Debrecen, Hajdú-Bihar

  • Somogy Megyei Kaposi Mac okato Korhoz

    Kaposvár

  • Somogy Megyei Kaposi Mór Oktató Kórház

    Kaposvár

  • Bács-Kiskun Megyei Kórház Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza

    Kecskemét, Bács-Kiskun county

  • Pécsi Tudományegyetem

    Pécs, Baranya

  • Szegedi Tudományegyetem

    Szeged, Csongrád megye

Other trials in Hungary

Poland7 sites

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespól Szpitali Miejskich

    Chorzów, Silesian Voivodeship

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, Pomeranian Voivodeship

  • Szpital Uniwersytecki w Krakowie

    Krakow, Lesser Poland Voivodeship

  • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K. Marcinkowskiego w Poznaniu

    Poznan, Greater Poland Voivodeship

  • Specjalistyczny Szpital Miejski im. Mikolaja Kopernika

    Torun, Kuyavian-Pomeranian Voivodeship

  • Instytut Hematologii i Transfuzjologii

    Warsaw, Masovian Voivodeship

  • Zamojski Szpital Niepubliczny Sp. z o.o.

    Zamość, Lublin Voivodeship

Other trials in Poland

Belgium6 sites

  • Ziekenhuis Netwerk Antwerpen

    Antwerp

  • Cliniques Universitaires Saint Luc

    Brussels

  • Universitair Ziekenhuis Brussel

    Brussels

  • Universitair Ziekenhuis Gent

    Ghent, Oost-vlaanderen

  • Universitair Ziekenhuis Leuven

    Leuven, Flemish Brabant

  • Cliniques Universitaires UCL de Mont-Godinne

    Yvoir, Namur

Other trials in Belgium

Czechia6 sites

  • Fakultní nemocnice Brno

    Brno

  • Fakultní nemocnice Hradec Králové

    Hradec Kralové, Vychodocesky KRAJ

  • Fakultní nemocnice Olomouc

    Olomouc, Severomoravsky KRAJ

  • FN Ostrava

    Ostrava, Severomoravsky KRAJ

  • Fakultní nemocnice Královské Vinohrady

    Prague, Prague

  • Všeobecná fakultní nemocnice v Praze

    Prague

Other trials in Czechia

Taiwan6 sites

  • Chang Gung Memorial Hospital

    Kaohsiung City

  • China Medical University Hospital

    Taichung

  • National Cheng-Kung University Hospital

    Tainan

  • National Taiwan University Hospital

    Taipei

  • Taipei Veterans General Hospital

    Taipei

  • Chang Gung Medical Foundation-LinKou Branch

    Taoyuan

Other trials in Taiwan

Israel5 sites

  • Rambam Health Corp.

    Haifa

  • Hadassah Medical Center

    Jerusalem

  • Meir Medical Center

    Kfar Saba

  • Tel Aviv Sourasky Medical Center

    Tel Aviv

  • The Chaim Sheba Medical Center at Tel Hashomer

    Tel HaShomer

Other trials in Israel

New Zealand5 sites

  • Christchurch Hospital

    Christchurch

  • Dunedin Hospital

    Dunedin

  • Auckland City Hospital

    Grafton, Aukland

  • North Shore Hospital

    North Shore, Auckland

  • Middlemore Hospital

    Otahuhu, Auckland

Other trials in New Zealand

Romania5 sites

  • Policlinica de Diagnostic Rapid SA, Compartiment Medical Oncologie-Hematologie

    Brasov

  • Spitalul Clinic Judetean de Urgenta Brasov (Bumbea, Horia)

    Brasov

  • Spitalul Universitar de Urgenta Bucuresti

    Bucharest, Bucharest

  • Institutul Clinic Fundeni

    Bucharest

  • Institutul Regional de Oncologie Iasi

    Iași

Other trials in Romania

Bulgaria4 sites

  • University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD

    Plovdiv

  • Military Medical Academy Hospital for Active Treatment

    Sofia, Sofia

  • Shato, Ead

    Sofia, Sofia

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

    Varna

Other trials in Bulgaria

Austria3 sites

  • Medizinische Universität Innsbruck

    Innsbruck, Tyrol

  • Krankenhaus der Elisabethinen Linz, I Interne Abteilung

    Linz, Upper Austria

  • Wilhelminenspital der Stadt Wien

    Vienna, State of Vienna

Other trials in Austria

Singapore3 sites

  • National University Cancer Institute

    Singapore

  • Singapore General Hospital

    Singapore

  • Singapore Oncology Consultants

    Singapore

Other trials in Singapore

Thailand3 sites

  • King Chulalongkorn Memorial Hospital

    Bangkok, Bangkok Metropolis

  • Ramathibodi Hospital

    Bangkok, Bangkok Metropolis

  • Srinagarind Hospital

    Khon Kaen

Other trials in Thailand

Greece1 site

  • Alexandra General Hospital

    Athens, Attica

Other trials in Greece

Slovakia1 site

  • Univerzitná nemocnica Bratislava

    Bratislava

Other trials in Slovakia

About this study

Official title: A Randomized, Open-label, Phase 3 Study of Carfilzomib Plus Dexamethasone vs. Bortezomib Plus Dexamethasone in Patients With Relapsed Multiple Myeloma

The primary objective of this study was to compare progression-free survival in patients with multiple myeloma who relapsed after 1 to 3 prior therapies treated with carfilzomib plus dexamethasone or bortezomib plus dexamethasone.

Keywords
multiple myeloma, relapsed multiple myeloma
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, Krypolis

    Carfilzomib is administered over 30 minutes as an infusion.

  • BortezomibDrug

    Also called Velcade

    Bortezomib is administered as a 3-5 second bolus IV injection or SC injection (in accordance with regulatory approval)

  • DexamethasoneDrug

    Tablet for oral administration; On days when carfilzomib or bortezomib was administered, the dexamethasone was to be given 30 minutes to 4 hours prior to the carfilzomib or bortezomib dose.

Study groups in NCT01568866
Study groupRoleWhat they receive
Carfilzomib plus DexamethasoneExperimentalParticipants received 20 mg/m² carfilzomib administered by intravenous (IV) infusion on Days 1 and 2 of Cycle 1, followed by 56 mg/m² on Days 8, 9, 15, and 16 of Cycle 1 and for each 28-day cycle thereafter. Additionally, participants received 20 mg dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28 day cycle.
Receives: Drug: Carfilzomib; Drug: Dexamethasone
Bortezomib plus DexamethasoneActive comparatorParticipants received bortezomib 1.3 mg/m² administered IV or subcutaneously (SC) on Days 1, 4, 8, and 11 of a 21-day cycle plus dexamethasone 20 mg administered on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.
Receives: Drug: Bortezomib; Drug: Dexamethasone

What is being measured

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

  1. Progression-free Survival

    Progression-free survival (PFS) was defined as the time from randomization to the earlier of disease progression or death due to any cause. Participants were evaluated for disease response and progression according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) as assessed by an Independent Review Committee (IRC).

    Median PFS was estimated using the Kaplan-Meier method. Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.

    Measured: From randomization until the data cut-off date of 10 November 2014; median follow-up time for PFS was 11.1.and 11.9 months in the bortezomib and carfilzomib arms respectively

Secondary outcomes (7)

  1. Overall Survival

    Overall survival (OS) is 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 at the patient's date of last contact (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 03 January 2017; median follow-up time for OS was 36.9 and 37.5 months for each treatment group respectively.

  2. Overall Response

    Disease response was evaluated according to the IMWG-URC by the IRC. Overall response was defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR) or stringent CR (sCR).

    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 end of treatment or the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group.

  3. Duration of Response

    Duration of response (DOR) was calculated for participants who achieved an sCR, CR, VGPR, or PR. Duration of response is defined as the time from first evidence of PR or better to confirmation of disease progression or death due to any cause. Median duration of response was estimated using the Kaplan-Meier method. Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.

    Measured: From randomization until the data cut-off date of 10 November 2014; median follow-up time for DOR was 9.4 and 10.4 months for each treatment group 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 study drug up to 30 days after the last dose of study drug as of the data cut-off date of 10 November 2014; median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group.

  5. Percentage of Participants With a Significant Reduction in Left Ventricular Ejection Fraction (LVEF)

    A significant reduction in LVEF was defined as a ≥ 10% decrease (absolute change) from baseline in participants whose baseline LVEF is ≤ 55%.

    For participants with LVEF > 55% at baseline, a significant change was defined as a decrease in LVEF to < 45%.

    Measured: Baseline and 24 weeks

  6. Change From Baseline in Right Ventricular Fractional Area Change (FAC)

    Right ventricular function was assessed by measuring fractional area change (FAC) on echocardiogram.

    Measured: Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group).

  7. Change From Baseline in Pulmonary Artery Systolic Pressure (PASP)

    Pulmonary artery pressure was measured using transthoracic echocardiogram.

    Measured: Baseline and Weeks 12, 24 and 36 and at end of treatment (median duration of treatment was 27 weeks in the bortezomib group and 40 weeks in the carfilzomib treatment group).

Timeline

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

  1. First posted2 Apr 2012 (estimated)
  2. Study start20 Jun 2012
  3. Primary completion10 Nov 2014
  4. Study completion5 Feb 2018

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
929 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01568866
Sponsor's protocol ID
2011-003
Other IDs
2012-000128-16
Acronym
ENDEAVOR
Status last verified
Nov 2022
First submitted
28 Mar 2012
Last updated
14 Nov 2022
Data monitoring committee
Yes

Publications

  • Moreau P, Joshua D, Chng WJ, Palumbo A, Goldschmidt H, Hajek R, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Aggarwal S, Feng S, Dimopoulos MA. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study. Leukemia. 2017 Jan;31(1):115-122. doi: 10.1038/leu.2016.186. Epub 2016 Jul 4.

    PubMed 27491641

  • Chng WJ, Goldschmidt H, Dimopoulos MA, Moreau P, Joshua D, Palumbo A, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Feng S, Aggarwal S, Hajek R. Carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed or refractory multiple myeloma by cytogenetic risk in the phase 3 study ENDEAVOR. Leukemia. 2017 Jun;31(6):1368-1374. doi: 10.1038/leu.2016.390. Epub 2016 Dec 27.

    PubMed 28025582

  • Dimopoulos MA, Goldschmidt H, Niesvizky R, Joshua D, Chng WJ, Oriol A, Orlowski RZ, Ludwig H, Facon T, Hajek R, Weisel K, Hungria V, Minuk L, Feng S, Zahlten-Kumeli A, Kimball AS, Moreau P. Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1327-1337. doi: 10.1016/S1470-2045(17)30578-8. Epub 2017 Aug 23.

    PubMed 28843768

  • Ludwig H, Dimopoulos MA, Moreau P, Chng WJ, Goldschmidt H, Hajek R, Facon T, Pour L, Niesvizky R, Oriol A, Rosinol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Palumbo A, Gillenwater HH, Mohamed N, Aggarwal S, Feng S, Joshua D. Carfilzomib and dexamethasone vs bortezomib and dexamethasone in patients with relapsed multiple myeloma: results of the phase 3 study ENDEAVOR (NCT01568866) according to age subgroup. Leuk Lymphoma. 2017 Oct;58(10):2501-2504. doi: 10.1080/10428194.2017.1298755. Epub 2017 Mar 17. No abstract available.

    PubMed 28306371

  • 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

  • Dimopoulos M, Siegel D, White DJ, Boccia R, Iskander KS, Yang Z, Kimball AS, Mezzi K, Ludwig H, Niesvizky R. Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR. Blood. 2019 Jan 10;133(2):147-155. doi: 10.1182/blood-2018-06-860015. Epub 2018 Nov 26.

    PubMed 30478094

  • Facon T, Niesvizky R, Mateos MV, Siegel D, Rosenbaum C, Bringhen S, Weisel K, Ho PJ, Ludwig H, Kumar S, Wang K, Obreja M, Yang Z, Klippel Z, Mezzi K, Goldrick A, Tekle C, Dimopoulos MA. Efficacy and safety of carfilzomib-based regimens in frail patients with relapsed and/or refractory multiple myeloma. Blood Adv. 2020 Nov 10;4(21):5449-5459. doi: 10.1182/bloodadvances.2020001965.

    PubMed 33166401

  • Hari P, Mateos MV, Abonour R, Knop S, Bensinger W, Ludwig H, Song K, Hajek R, Moreau P, Siegel DS, Feng S, Obreja M, Aggarwal SK, Iskander K, Goldschmidt H. Efficacy and safety of carfilzomib regimens in multiple myeloma patients relapsing after autologous stem cell transplant: ASPIRE and ENDEAVOR outcomes. Leukemia. 2017 Dec;31(12):2630-2641. doi: 10.1038/leu.2017.122. Epub 2017 Apr 25.

    PubMed 28439109

  • Leleu X, Martin TG, Einsele H, Lyons RM, Durie BGM, Iskander KS, Ailawadhi S. Role of Proteasome Inhibitors in Relapsed and/or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019 Jan;19(1):9-22. doi: 10.1016/j.clml.2018.08.016. Epub 2018 Sep 5.

    PubMed 30287200

  • Ludwig H, Moreau P, Dimopoulos MA, Mateos MV, Kaiser M, Hajek R, Feng S, Cocks K, Buchanan J, Weisel K. Health-related quality of life in the ENDEAVOR study: carfilzomib-dexamethasone vs bortezomib-dexamethasone in relapsed/refractory multiple myeloma. Blood Cancer J. 2019 Feb 22;9(3):23. doi: 10.1038/s41408-019-0181-0.

    PubMed 30796199

  • Mateos MV, Goldschmidt H, San-Miguel J, Mikhael J, DeCosta L, Zhou L, Obreja M, Blaedel J, Szabo Z, Leleu X. Carfilzomib in relapsed or refractory multiple myeloma patients with early or late relapse following prior therapy: A subgroup analysis of the randomized phase 3 ASPIRE and ENDEAVOR trials. Hematol Oncol. 2018 Apr;36(2):463-470. doi: 10.1002/hon.2499. Epub 2018 Feb 15.

    PubMed 29446103

  • Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.

    PubMed 32108443

  • Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, Zahlten-Kumeli A, Sersch MA, Li J, Huang M, Lee JH. Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials. Int J Hematol. 2019 Oct;110(4):466-473. doi: 10.1007/s12185-019-02704-z. Epub 2019 Aug 6.

    PubMed 31388932

  • Goldschmidt H, Moreau P, Ludwig H, Niesvizky R, Chng WJ, Joshua D, Weisel K, Spencer A, Orlowski RZ, Feng S, Iskander KS, Dimopoulos MA. Carfilzomib-dexamethasone versus subcutaneous or intravenous bortezomib in relapsed or refractory multiple myeloma: secondary analysis of the phase 3 ENDEAVOR study. Leuk Lymphoma. 2018 Jun;59(6):1364-1374. doi: 10.1080/10428194.2017.1376743. Epub 2017 Sep 22.

    PubMed 28937327

  • Jakubowiak AJ, Houisse I, Majer I, Benedict A, Campioni M, Panjabi S, Ailawadhi S. Cost-effectiveness of carfilzomib plus dexamethasone compared with bortezomib plus dexamethasone for patients with relapsed or refractory multiple myeloma in the United States. Expert Rev Hematol. 2017 Dec;10(12):1107-1119. doi: 10.1080/17474086.2017.1391088.

    PubMed 29027825

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Carfilzomib, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Amgen at 241 sites in 27 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 22 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 14 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 241 sites in United States, Japan, Australia, Germany, Italy and 22 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 11 Dec 2015). 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 10 November 2014; median follow-up time for PFS was 11.1.and 11.9 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 NCT01568866, which also lists 21 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 14 Nov 2022.

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