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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01568866
Other study ID # 2011-003
Secondary ID 2012-000128-16
Status Completed
Phase Phase 3
First received
Last updated
Start date June 20, 2012
Est. completion date February 5, 2018

Study information

Verified date November 2022
Source Amgen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


Recruitment information / eligibility

Status Completed
Enrollment 929
Est. completion date February 5, 2018
Est. primary completion date November 10, 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Multiple myeloma with relapsing or progressing disease at study entry. 2. 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). 3. 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. 4. 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). 5. 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). 6. 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. 7. Males and females = 18 years of age. 8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2. 9. 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. 10. Left ventricular ejection fraction (LVEF) = 40%. 11. Absolute neutrophil count (ANC) = 1000/mm³ within 21 days prior to randomization. Screening ANC should be independent of growth factor support for = 1 week. 12. 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. 13. 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. 14. 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. 15. Written informed consent in accordance with federal, local, and institutional guidelines. 16. 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). 17. 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. Exclusion Criteria: 1. Multiple Myeloma of IgM subtype. 2. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization. 3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). 4. Plasma cell leukemia or circulating plasma cells = 2 × 10^9/L. 5. Waldenstrom's Macroglobulinemia. 6. Patients with known amyloidosis. 7. Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to randomization. 8. Patients randomized or previously randomized in any other Onyx-Sponsored Phase 3 trial. 9. 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). 10. Immunotherapy within 21 days prior to randomization. 11. Major surgery (excluding kyphoplasty) within 28 days prior to randomization. 12. 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. 13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to randomization. 14. 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). 15. Patients with known cirrhosis. 16. 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 17. Patients with myelodysplastic syndrome. 18. Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days prior to randomization. 19. Female patients who are pregnant or lactating. 20. Known history of allergy to Captisol(a cyclodextrin derivative used to solubilize carfilzomib). 21. Patients with hypersensitivity to carfilzomib, Velcade, boron, or mannitol. 22. Patients with contraindication to dexamethasone. 23. 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. 24. Ongoing graft-vs-host disease. 25. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Carfilzomib
Carfilzomib is administered over 30 minutes as an infusion.
Bortezomib
Bortezomib is administered as a 3-5 second bolus IV injection or SC injection (in accordance with regulatory approval)
Dexamethasone
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.

Locations

Country Name City State
Australia Royal Adelaide Hospital Adelaide South Australia
Australia Box Hill Hospital Box Hill Victoria
Australia Royal Prince Alfred Hospital Camperdown New South Wales
Australia Monash Medical Centre Clayton Victoria
Australia St. Vincent's Public Hospital Sydney Darlinghurst New South Wales
Australia Saint Vincent's Hospital East Melbourne Victoria
Australia Western Hospital Footscray Victoria
Australia Fremantle Hospital Fremantle Western Australia
Australia Royal Brisbane and Women's Hospital Herston Queensland
Australia Saint George Hospital Kogarah New South Wales
Australia Liverpool Hospital Liverpool New South Wales
Australia The Alfred Hospital Melbourne Victoria
Australia Royal Perth Hospital Perth Western Australia
Australia Royal North Shore Hospital Saint Leonards New South Wales
Australia Haematology & Oncology Clinics of Australia South Brisbane Queensland
Australia Haematology and Oncology Clinics of Australia at Chermside South Brisbane Queensland
Australia Haematology and Oncology Clinics of Australia at Wesley South Brisbane Queensland
Australia Sunshine Hospital St. Albans Victoria
Australia Calvary Mater Newcastle Waratah New South Wales
Australia Westmead Hospital Westmead New South Wales
Australia The Queen Elizabeth Hospital Woodville South Australia
Austria Medizinische Universität Innsbruck Innsbruck Tyrol
Austria Krankenhaus der Elisabethinen Linz, I Interne Abteilung Linz Upper Austria
Austria Wilhelminenspital der Stadt Wien Wien Vienna
Belgium Ziekenhuis Netwerk Antwerpen Antwerp
Belgium Cliniques Universitaires Saint Luc Brussels
Belgium Universitair Ziekenhuis Brussel Brussels
Belgium Universitair Ziekenhuis Gent Ghent Oost-vlaanderen
Belgium Universitair Ziekenhuis Leuven Leuven Flemish Brabant
Belgium Cliniques Universitaires UCL de Mont-Godinne Yvoir Namur
Brazil Hemocentro Campinas-Unicamp Campinas SAO Paulo
Brazil Liga Norte Riograndense Contra o Câncer Natal RIO Grande DO Norte
Brazil Clínica de Oncologia de Porto Alegre Porto Alegre RIO Grande DO SUL
Brazil Hospital de Clínicas de Porto Alegre Porto Alegre RIO Grande DO SUL
Brazil Hospital São Lucas da PUCRS Porto Alegre RIO Grande DO SUL
Brazil Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro Rio de Janeiro
Brazil Instituto Centros Oncológicos Integrados de Educação e Pesquisa Rio de Janeiro
Brazil Instituto Nacional do Câncer-INCA Rio de Janeiro
Brazil Irmandade da Santa Casa de Misericórdia de São Paulo São Paulo
Bulgaria University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD Plovdiv
Bulgaria Military Medical Academy Hospital for Active Treatment Sofia Sofiya
Bulgaria Shato, Ead Sofia Sofiya
Bulgaria Multiprofile Hospital for Active Treatment, "Sveta Marina'' Varna
Canada University of Alberta Hospital Edmonton Alberta
Canada Queen Elizabeth II Health Science Centre Halifax Nova Scotia
Canada British Columbia Cancer Agency Kelowna British Columbia
Canada London Health Sciences Centre London Ontario
Canada Hopital Maisonneuve-Rosemont Montréal Quebec
Canada The Ottawa Hospital Regional Cancer Centre Ottawa Ontario
Canada Saint John Regional Hospital Saint John New Brunswick
Canada Windsor Regional Hospital Windsor Ontario
Czechia Fakultní nemocnice Brno Brno
Czechia Fakultní nemocnice Hradec Králové Hradec Kralové Vychodocesky KRAJ
Czechia Fakultní nemocnice Olomouc Olomouc Severomoravsky KRAJ
Czechia FN Ostrava Ostrava Severomoravsky KRAJ
Czechia Všeobecná fakultní nemocnice v Praze Praha
Czechia Fakultní nemocnice Královské Vinohrady Praha 10 Praha
France Centre Hospitalier de la Cote Basque Bayonne Aquitaine
France Centre Hospitalier Universitaire Brest Brest Cedex Bretagne
France Centre Hospitalier de Versailles Le Chesnay Ile-de-france
France Hôpital Claude Huriez Lille Cedex NORD Pas-de-calais
France Institut Paoli Calmettes Marseille Cedex 9 Provence Alpes COTE D'azur
France Hopital Hotel-Dieu - Service d'Hematologie Nantes Cedex 1
France Hôpital Hôtel-Dieu Nantes cedex 1 PAYS DE LA Loire
France Hôpital Saint Louis Paris Ile-de-france
France Hôpital Saint-Antoine Paris Ile-de-france
France Centre Hospitalier Lyon Sud Pierre Bénite Cedex Rhone-alpes
France Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou Rennes Cedex 9 Bretagne
France Centre Henri-Becquerel Rouen Cedex 1 Haute-normandie
Germany Universitätsklinikum Aachen Aachen Nordrhein-westfalen
Germany Klinikum Chemnitz gGmbH Chemnitz Sachsen
Germany Universitätsklinikum Carl Gustav Carus, Med. Klinik und Poliklinik I Dresden Sachsen
Germany Universitatsklinikum Freiburg Freiburg
Germany Universitätsklinikum Hamburg Eppendorf Hamburg
Germany Medizinische Hochschule Hannover Hannover Niedersachsen
Germany Universitätsklinik Heidelberg Heidelberg Baden-wuerttemberg
Germany Universitätsklinikum des Saarlandes Homburg / Saar Saarland
Germany Universitätsklinikum Jena Jena Thuringen
Germany Universitätsklinikum Leipzig Leipzig Sachsen
Germany Universitätsmedizin der Johannes Gutenberg Universität Mainz Rheinland-pfalz
Germany Universitätsklinikum Münster Münster Nordrhein-westfalen
Germany Universitätsklinikum Tübingen Tübingen Baden-wuerttemberg
Germany Universitätsklinikum Ulm Ulm Baden-wuerttemberg
Germany Medizinische Klinik der Universität Würzburg Würzburg Bayern
Greece Alexandra General Hospital Athens Attica
Hungary Egyesített Szent István és Szent László Kórház-Rendelointézet Budapest
Hungary Debreceni Egyetem Klinikai Központ Debrecen Hajdu-bihar
Hungary Somogy Megyei Kaposi Mac okato Korhoz Kaposvár
Hungary Somogy Megyei Kaposi Mór Oktató Kórház Kaposvár
Hungary Bács-Kiskun Megyei Kórház Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza Kecskemét Bacs-kiskun
Hungary Pécsi Tudományegyetem Pécs Baranya
Hungary Szegedi Tudományegyetem Szeged Csongrad
Israel Rambam Health Corp. Haifa
Israel Hadassah Medical Center Jerusalem
Israel Meir Medical Center Kfar Saba
Israel Tel Aviv Sourasky Medical Center Tel Aviv
Israel The Chaim Sheba Medical Center at Tel Hashomer Tel Hashomer
Italy Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona Ancona
Italy Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi Bologna
Italy Azienda Ospedaliera Spedali Civili di Brescia Brescia
Italy IRCCS Azienda Ospedaliera Universitaria San Martino Genova
Italy Azienda Ospedaliera Universitaria Maggiore della Carità Novara
Italy Azienda Ospedaliero-Univesitaria San Luigi Gonzaga Orbassano Torino
Italy Azienda Unità Sanitaria Locale di Piacenza-Ospedale Guglielmo da Saliceto Piacenza
Italy Azienda Ospedaliera Pisana Ospedale Santa Chiara Pisa
Italy IRCCS Centro di Riferimento Oncologico di Basilicata di Rionero in Vulture Rionero in Vulture Potenza
Italy Aienda Policknico Umberto I di Roma Roma
Italy Azienda Policknico Umberto l di Roma Roma
Italy Università Tor Vergata Ospedale Sant Eugenio Roma
Italy Azienda Ospedaliera Universitaria Senese - Policlinico S. Maria alle Scotte Siena
Italy Azienda Ospedaliera Città della Salute e della Scienza di Torino Torino
Japan National Cancer Center Hospital Chuo-ku Tokyo
Japan Kyushu University Hospital Fukuoka
Japan National Hospital Organization Kyushu Cancer Center Fukuoka-city Fukuoka
Japan Tokai University Hospital Isehara Kanagawa
Japan Saitama Medical Center Kawagoe Saitama
Japan Kobe City Medical Center General Hospital Kobe Hyogo
Japan The Cancer Institute Hospital Of Japanese Foundation For Cancer Research Koto-ku Tokyo
Japan Social Insurance Kyoto Hospital of All Japan Federation of Social Insurance Associations Kyoto
Japan University Hospital, Kyoto Prefectural University of Medicine Kyoto
Japan Gunma University Hospital Maebashi Gunma
Japan Nagoya City University Hospital Nagoya City Aichi
Japan Niigata Cancer Center Hospital Niigata-city Niigata
Japan Ogaki Municipal Hospital Ogaki City Gifu
Japan National Hospital Organization Okayama Medical Center Okayama
Japan Sapporo Medical University Hospital Sapporo Hokkaido
Japan National Hospital Organization Nishigunma National Hospital Shibukawa Gunma
Japan Toranornon Hospital Shinagawa Tokyo
Japan Tokyo Medical University Hospital Shinjuku Tokyo
Japan Osaka University Hospital Suita Osaka
Japan National Hospital Organization Disaster Medical Center Tachikawa Tokyo
Japan Tokushima Prefectural Central Hospital Tokushima
Japan Japanese Red Cross Medical Center Tokyo
Japan Toyohashi Municipal Hospital Toyohashi Aichi
Japan Tochigi Cancer Center Utsunomiya Tochigi
Korea, Republic of Pusan National University Hospital Busan Gyeongsangnam-Do
Korea, Republic of Kyungpook National University Hospital Daegu
Korea, Republic of Gachon University Gil Medical Center Incheon Gyeonggi-Do
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 Seoul Saint Mary's Hospital Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
New Zealand Christchurch Hospital Christchurch
New Zealand Dunedin Hospital Dunedin
New Zealand Auckland City Hospital Grafton Aukland
New Zealand North Shore Hospital North Shore City Auckland
New Zealand Middlemore Hospital Otahuhu Auckland
Poland Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespól Szpitali Miejskich Chorzów Slaskie
Poland Uniwersyteckie Centrum Kliniczne Gdansk Pomorskie
Poland Szpital Uniwersytecki w Krakowie Krakow Malopolskie
Poland Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im K. Marcinkowskiego w Poznaniu Poznan Wielkopolskie
Poland Specjalistyczny Szpital Miejski im. Mikolaja Kopernika Torun Kujawsko-Pomorskie
Poland Instytut Hematologii i Transfuzjologii Warszawa Mazowieckie
Poland Zamojski Szpital Niepubliczny Sp. z o.o. Zamosc Lubelskie
Romania Policlinica de Diagnostic Rapid SA, Compartiment Medical Oncologie-Hematologie Brasov
Romania Spitalul Clinic Judetean de Urgenta Brasov (Bumbea, Horia) Brasov
Romania Spitalul Universitar de Urgenta Bucuresti Bucharest Bucuresti
Romania Institutul Clinic Fundeni Bucuresti
Romania Institutul Regional de Oncologie Iasi Iasi
Russian Federation Republican Clinical Hospital #1 Izhevsk
Russian Federation City Clinical Hospital n.a. S. P. Botkin Moscow
Russian Federation Non-state Healthcare Institution "N.A. Semashko Central Clinical Hospital #2 of JSC "Russian Railway Moscow
Russian Federation Ryazan Regional Clinical Hospital Ryazan
Russian Federation Clinical Hospital Number 31 Saint Petersburg
Russian Federation Federal Almazov Medical Research Centre Saint Petersburg
Russian Federation FGU Russian Scientific Research Institute of Hematology and Transfusiology Saint Petersburg
Russian Federation First Saint Petersburg I.P. Pavlov State Medical University Saint Petersburg
Russian Federation GUZ Samara Regional Clinical Hospital n.a. M.I. Kalinin Samara
Singapore National University Cancer Institute Singapore
Singapore Singapore General Hospital Singapore
Singapore Singapore Oncology Consultants Singapore
Slovakia Univerzitná nemocnica Bratislava Bratislava
Spain Hospital Universitari Germans Trias i Pujol Badalona Barcelona
Spain Hospital Clinic I Provincial de Barcelona Barcelona
Spain Institut Universitari Dexeus Barcelona
Spain Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro Madrid
Spain Hospital Universitario 12 de Octubre Madrid
Spain Hospital Universitario La Princesa Madrid
Spain Hospital Son Llàtzer Palma de Mallorca Baleares
Spain Hospital Clínico Universitario de Salamanca Salamanca
Spain Hospital Universitario Virgen del Rocio Sevilla
Spain Hospital Universitari i Politecnic La Fé de Valencia Valencia
Taiwan Chang Gung Memorial Hospital Kaohsiung
Taiwan China Medical University Hospital Taichung
Taiwan National Cheng-Kung University Hospital Tainan
Taiwan National Taiwan University Hospital Taipei
Taiwan Taipei Veterans General Hospital Taipei
Taiwan Chang Gung Medical Foundation-LinKou Branch Tao-Yuan
Thailand King Chulalongkorn Memorial Hospital Bangkok Bangkok Metropolis
Thailand Ramathibodi Hospital Bangkok Bangkok Metropolis
Thailand Srinagarind Hospital Khon Kaen
Ukraine Cherkassy Regional Oncology Center Cherkassy
Ukraine City Hematology Center Dnepropetrovsk Dnipropretrovsk
Ukraine MI "Dnipropetrovsk City Multifield Clinical Hospital #4" of Dnipropetrovsk Regional Council", City Hematology Center Dnipropetrovsk
Ukraine Institute of Urgent and Reparative Surgury of Ukraine Academy of Medical Sciences Donetsk
Ukraine Municipal Institution of Health Protection "Clinical Hospital #8" Kharkov Kharkiv
Ukraine Khmelnytsky Regional Clinical Hospital Khmelnytsky
Ukraine Khmelnytsky Regional Hospital, Department of Hematology Khmelnytsky
Ukraine National Institute of Cancer, Oncohematology Department Kiev
Ukraine Kyiv Bone Marrow Transplantation Center Kyiv
Ukraine Lviv Regional Oncology Dispensary Lviv
Ukraine Lviv State Oncology Regional Treatment-Prophylactic Center, Department of Chemotherapy Lviv
Ukraine Regional Clinical Hospital Mykolayiv
United Kingdom Royal Free Hospital London England
United Kingdom University College Hospital London England
United Kingdom Manchester Royal Infirmary Manchester England
United Kingdom Nottingham University Hospitals NHS Trust Nottingham England
United Kingdom Churchill Hospital Oxford England
United Kingdom Derriford Hospital Plymouth England
United Kingdom Royal Hallamshire Hospital Sheffield England
United Kingdom Royal Marsden Hospital Surrey England
United Kingdom Royal Wolverhampton Hospitals Trust Wolverhampton England
United States University of Michigan Ann Arbor Michigan
United States Winship Cancer Institute Atlanta Georgia
United States Center for Cancer and Blood Disorders Bethesda Maryland
United States Montefiore Medical Center Bronx New York
United States Providence St. Joseph Medical Center Burbank California
United States Gabrail Cancer Center Canton Ohio
United States The Christ Hospital Cincinnati Ohio
United States Colorado Blood Cancer Institute Denver Colorado
United States Hematology/Oncology Associates of SC Greenville South Carolina
United States Hackensack University Medical Ctr Hackensack New Jersey
United States MD Anderson Houston Texas
United States The Methodist Cancer Center Houston Texas
United States Hematology Oncology of Indiana, PC Indianapolis Indiana
United States University of Kansas Kansas City Missouri
United States UCSD Moore Cancer Center La Jolla California
United States UCLA Medical Center Los Angeles California
United States MAB Oncology/Hematology Melbourne Florida
United States Vanderbilt Ingram Cancer Center Nashville Tennessee
United States Clinical Research Alliance Inc. New York New York
United States Weill Cornell Medical College New York New York
United States Western Pennsylvania Hospital Pittsburgh Pennsylvania
United States Associates in Oncology/Hematology PC Rockville Maryland
United States University of Utah School of Medicine Salt Lake City Utah
United States Central Coast Medical Oncology Group Santa Maria California
United States Scott & White Memorial Hospital Temple Texas
United States Palm Beach Cancer Institute West Palm Beach Florida
United States Wake Forest University Health Sciences, Section on Hematology and Oncology Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Romania,  Russian Federation,  Singapore,  Slovakia,  Spain,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

References & Publications (18)

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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. Erratum in: Lancet Oncol. 2017 Oct;18(10):e562. — View Citation

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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. — View Citation

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. — View Citation

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. — View Citation

Jakubowiak AJ, Houisse I, Májer I, Benedict Á, 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. — View Citation

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. Review. — View Citation

Ludwig H, Dimopoulos MA, Moreau P, Chng WJ, Goldschmidt H, Hájek R, Facon T, Pour L, Niesvizky R, Oriol A, Rosiñol 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. — View Citation

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. — View Citation

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. — View Citation

Moreau P, Joshua D, Chng WJ, Palumbo A, Goldschmidt H, Hájek R, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosiñol 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. — View Citation

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/m(2) ) vs twice-weekly (56 mg/m(2) ) 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. — View Citation

Orlowski RZ, Moreau P, Niesvizky R, Ludwig H, Oriol A, Chng WJ, Goldschmidt H, Yang Z, Kimball AS, Dimopoulos M. Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups. Clin Lymphoma Myeloma Leuk. 2019 Aug;19(8):522-530.e1. doi: 10.1016/j.clml.2019.04.018. Epub 2019 May 2. — View Citation

Weisel K, Majer I, DeCosta L, Oriol A, Goldschmidt H, Ludwig H, Campioni M, Szabo Z, Dimopoulos M. Carfilzomib and dexamethasone versus eight cycles of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma: an indirect comparison using data from the phase 3 ENDEAVOR and CASTOR trials. Leuk Lymphoma. 2020 Jan;61(1):37-46. doi: 10.1080/10428194.2019.1648806. Epub 2019 Oct 22. — View Citation

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* Note: There are 18 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
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 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.
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.
Secondary 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.
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.
Secondary 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. 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.
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 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.
Secondary 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%.
Baseline and 24 weeks
Secondary Change From Baseline in Right Ventricular Fractional Area Change (FAC) Right ventricular function was assessed by measuring fractional area change (FAC) on echocardiogram. 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).
Secondary Change From Baseline in Pulmonary Artery Systolic Pressure (PASP) Pulmonary artery pressure was measured using transthoracic echocardiogram. 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).
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