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

Multiple Myeloma Clinical Trial

— ENDEAVOR  

Official title:

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

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
• 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
• 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

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 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. — View Citation

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

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. — View Citation

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

Weisel K, Mateos MV, Gay F, Delforge M, Cook G, Szabo Z, Desgraz R, DeCosta L, Moreau P. Efficacy and safety profile of deep responders to carfilzomib-based therapy: a subgroup analysis from ASPIRE and ENDEAVOR. Leukemia. 2021 Jun;35(6):1732-1744. doi: 10.1038/s41375-020-01049-5. Epub 2020 Oct 16. — View Citation

* Note: There are 18 references in all — Click 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).

External Links

•   AmgenTrials clinical trials website