Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma

A Randomized, Multicenter, Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma

The primary objective was to compare progression-free survival in adults with relapsed multiple myeloma who are receiving CRd vs participants receiving Rd in a randomized multicenter setting.

Study Overview

• Status: Completed
• Conditions: Relapsed Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Dexamethasone; Drug: Carfilzomib

Detailed Description

This is a Phase 3, randomized, open-label, multicenter study comparing two treatment regimens for adults with relapsed multiple myeloma. Eligible subjects will be randomized in a 1:1 ratio to receive either the control Rd or CRd. Randomization will be stratified by β2 microglobulin levels (< vs ≥ 2.5 mg/L), prior bortezomib (no vs yes), and prior lenalidomide (no vs yes). Participants will receive the treatment determined by randomization in 28-day cycles until disease progression or unacceptable toxicity (whichever occurs first).

• Study Type: Interventional
• Enrollment (Actual): 792
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • Medizinische Universitat Wien
  • Wien, Austria, 1171
    • Wilhelminspital der Stadt Wien, Zentrum fur Onkologie und Hamatologie
• Belgium
  • Antwerpen, Belgium, 2060
    • Ziekenhuisnetwerk Antwerpen - AZ Stuivenberg
  • Brugge, Belgium, 8000
    • AZ Sint-Jan AV
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Bruxelles, Belgium, 1000
    • Institut Jules Bordet
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-luc
  • Leuven, Belgium, 3000
    • UZ Leuven
• Bulgaria
  • Pleven, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment, "Dr. Georgi Stranski"
  • Plovdiv, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment "Sveti Georgi"
  • Sofia, Bulgaria, 1606
    • Military Medical Academy Multiprofile Hospital for Active Treatment
  • Sofia, Bulgaria, 1756
    • Specialized Hospital for Active Treatment of Hematological Diseases
  • Varna, Bulgaria, 9010
    • Multiprofile Hospital for Active Treatment "Sveta Marina"
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • University of Alberta, Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1B 3V6
      • General Hospital, Health Sciences Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • McGill University Health Center, Royal Victoria Hospital
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B. Davis - Jewish General Hospital
• Czechia
  • Brno, Czechia, 625 00
    • University Hospital Brno, Department of Internal Medicine - Hematooncology
  • Hradec Kralove, Czechia, 500 05
    • University hospital Hradec Králové
  • Olomouc, Czechia, 775 20
    • University Hospital Olomouc
  • Praha 10, Czechia, 100 34
    • University Hospital Kralovske Vinohrady - Prague
  • Praha 2, Czechia, 128 08
    • General University Hospital Prague
• France
  • Clamart, France, 92140
    • Hospital Antoine Beclere
  • Le Mans, France, 72000
    • Clinique Victor Hugo - Centre Jean Bernard
  • Lille, France, 59037
    • Hopital Claude Huriez
  • Mulhouse, France, 68070
    • CH de Mulhouse, Hopital Emile Muller
  • Nantes, France, 44093
    • CHU Nantes Hôtel Dieu
  • Paris, France, 75012
    • Hopital Saint-Antoine
  • Paris, France, 75015
    • Groupe Hospitalier Necker - Enfants Malades
  • Toulouse, France, 31100
    • Cancer Institut Universitaire de Toulouse-Oncopole (iUCT)
  • Vandoeuvre-Les-Nancy, France, 54511
    • Hopitaux de Brabois
• Germany
  • Dusseldorf, Germany, 40225
    • University of Dusseldorf
  • Frankfurt am Main, Germany, 60488
    • Krankenhaus Nordwest
  • Hamburg, Germany, 20246
    • University of Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • Universitat Heidelberg
  • Koblenz, Germany, 56068
    • Stiftungsklinikum Mittelrhein
  • Munchen, Germany, 81377
    • LMU Klinikum der Universität
  • Munster, Germany, 48129
    • Universitatsklinikum Munster
  • Wurzburg, Germany, 97080
    • Universitatsklinikum Wurzburg
• Greece
  • Athens, Greece, 11528
    • Alexandra Hospital
  • Patras, Greece, 26500
    • University General Hospital of Patras
• Hungary
  • Budapest, Hungary, H-1097
    • St. Istvan and St. Laszlo Hospital of Budapest
  • Debrecen, Hungary, H-4032
    • University of Debrecen, Medical and Health Science Center
  • Gyor, Hungary, H-9032
    • Petz Aladár County Teaching Hospital
  • Gyula, Hungary, H-5700
    • Bekes County Pandy Kalman Hospital
  • Kaposvar, Hungary, H-7400
    • Kaposi Mór County Teaching Hospital
  • Pecs, Hungary, H-7624
    • University of Pecs
  • Szeged, Hungary, H-6720
    • University of Szeged, Albert Szent-Gyorgi Clinical Center
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center, Ein Kerem
  • Nahariya, Israel, 22100
    • Western Gailee Hospital - Nahariya
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center
  • Ramat Gan, Israel, 52621
    • The Chaim Sheba Medical Center
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
• Italy
  • Milano, Italy, 20162
    • Azienda Ospedallera Niguarda Ca Granda
  • Novara, Italy, 28100
    • Azienda Ospedllero Maggiore della Carita
  • Pisa, Italy, 56216
    • Azienda Ospedaliera Pisana Ospendale Santa Chiara - Main
  • Roma, Italy, 00144
    • Ospedale S. Eugenio
  • Torino, Italy, 10126
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC, Department of Haematology
• Poland
  • Gdansk, Poland, 80-952
    • University Clinical Centre, Department of Hematologii Transplantologii
  • Gorzow Wielkopolski, Poland, 66-400
    • Samodzielny Publ. Szp. Wojewodzki w Gorzow Wlkp.
  • Katowice, Poland, 40-027
    • Independent Public Teaching Hospital of Medical University of Silesia in Katowice
  • Lodz, Poland, 93-510
    • Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz
  • Suwalki, Poland, 16-400
    • Szpital Wojewwodzki im. dr Ludwika Rydygiera w Suwalkach
  • Torun, Poland, 87-100
    • Nicolaus Copernicus Municipal Specialist Hospital
  • Warszawa, Poland, 02-781
    • Maria Sklodowska-Curie Institute of Oncology
  • Zamosc, Poland, 22-400
    • Zamojski Non-Public Hospital
• Romania
  • Bucharest, Romania, 022328
    • Fundeni Clinical Institute, "Stefan Berceanu" Center for Hematology and Bone Marrow Transplantation
  • Bucharest, Romania, 030-171
    • Coltea Clinical Hospital
  • Bucharest, Romania, 050098
    • Bucharest University Emergency Hospital
  • Iasi, Romania, 700483
    • Regional Institute of Iasi
• Russian Federation
  • Izhevsk, Russian Federation, 426039
    • First Republican Clinical Hospital under the Ministry of Healthcare of the Republic of Udmurtia
  • Moscow, Russian Federation, 115478
    • Federal State Budgetary Scientific Institution: N.N. Blokhin Russian Cancer Research Center
  • Moscow, Russian Federation, 125101
    • Moscow State Medical Institution Municipal City Clinical Hospital n.a. S.P. Botkin
  • Moscow, Russian Federation, 125167
    • Federal State Budget Institution: Hematology Research Center under MoH
  • St. Petersburg, Russian Federation, 191024
    • FSBI: Russian Research Institute of Hematology and Blood Transfusion under the Ferderal Agency for M&B
  • St. Petersburg, Russian Federation, 197022
    • State Higher Educational Institution: St Petersburg State Medical University n.a.I.P Pavlov
  • St. Petersburg, Russian Federation, 197101
    • SHEI: First St. Petersburg State Medical University N.a.I.P Pavlov under MoH, Clinic of Bone Marrow Transplant
  • St. Petersburg, Russian Federation, 197341
    • Federal State Budget Institute: Federal Almalov Medical Research Centre under Ministry of Healthcare
  • Komi Republic
    • Syktyvkar, Komi Republic, Russian Federation, 167904
      • State Medical Institution Komi Republican Oncological Center
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia, Clinic of Hematology
  • Belgrade, Serbia, 11000
    • Clinical Hospital Center Bezanijska Kosa
  • Belgrade, Serbia, 11000
    • Military Medical Academy, Clinic of Hematology
  • Nis, Serbia, 18 000
    • Clinical Center Nis, Clinic of Hematology
  • Novi Sad, Serbia, 21 000
    • Clinical Center of Vojvodina, Clinic of Hematology
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitario Germans Trias i Pujol
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • San Sebastian, Spain, 20014
    • Hospital Donostia
  • Valencia, Spain, 46026
    • Hospital Universitario y Politeecnico La Fe
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Sweden
  • Goteborg, Sweden, SE-41345
    • Sahlgrenska Universitetssjukhuset
  • Stockholm, Sweden, SE-14186
    • Karolinska Universitetsjukhuset i Huddinge
  • Stockholm, Sweden, SE-17176
    • Karolinska Universitetssjukhuset Solna, Hematologiskt Centrum
• United Kingdom
  • London, United Kingdom, SW17 0QT
    • St. Georges Hospital
  • London, United Kingdom, EC1A 7BE
    • St. Bartholomew's Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hampstead
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals (City Campus)
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
  • Wolverhampton, United Kingdom, WV10 OQP
    • The Royal Wolverhampton Hospital NHS Trust
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • California
    • Burbank, California, United States, 91505
      • Providence St. Joseph Medical Center
    • Santa Rosa, California, United States, 94503
      • St. Jude Hospital Yorba Linda dba; St. Joseph Heritage Healthcare
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Lecanto, Florida, United States, 34461
      • Cancer and Blood Disease Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • The University of Michigan - Comprehensive Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Clinical Cancer Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Associates in Oncology and Hematology
  • Texas
    • Amarillo, Texas, United States, 79106
      • The Don & Sybil Harrington Cancer Center
    • Dallas, Texas, United States, 75246
      • Baylor Sammons Cancer Center
    • Dallas, Texas, United States, 75390-8565
      • UT Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • The University of Texas, MD Anderson Cancer Center
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert & Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Symptomatic multiple myeloma

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

   • Serum M-protein ≥ 0.5 g/dL
   • Urine Bence-Jones protein ≥ 200 mg/24 hours
   • For immunoglobulin A (IgA) patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL)
3. Prior treatment with at least one, but no more than three, regimens for multiple myeloma
4. Documented relapse or progressive disease on or after any regimen
5. Achieved a response to at least one prior regimen
6. Age ≥ 18 years
7. Life expectancy ≥ 3 months
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
9. Adequate hepatic function, with serum alanine aminotransferase (ALT) ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 21 days prior to randomization
10. Absolute neutrophil count ≥ 1.0 × 10^9/L within 21 days prior to randomization
11. Hemoglobin ≥ 8 g/dL (80 g/L) within 21 days prior to randomization
12. Platelet count ≥ 50 × 10^9/L (≥ 30 × 10^9/L if myeloma involvement in the bone marrow is > 50%) within 21 days prior to randomization
13. Creatinine clearance (CrCl) ≥ 50 mL/minute within 21 days prior to randomization
14. Written informed consent in accordance with federal, local, and institutional guidelines
15. Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception
16. Male subjects must agree to practice contraception

Exclusion Criteria:

1. If previously treated with bortezomib (alone or in combination), progression during treatment

2. If previously treated with a lenalidomide and dexamethasone (len/dex) combination:

   • Progression during the first 3 months of initiating treatment
   • Any progression during treatment if the len/dex combination was the subject's most recent line of therapy
3. Discontinuation of previous lenalidomide or dexamethasone due to intolerance; subjects intolerant to bortezomib are not excluded
4. Prior carfilzomib treatment
5. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
6. Waldenström's macroglobulinemia or IgM myeloma
7. Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
8. Chemotherapy or investigational agent within 3 weeks prior to randomization or antibody therapy within 6 weeks prior to randomization
9. Radiotherapy to multiple sites or immunotherapy/antibody therapy within 28 days prior to randomization; localized radiotherapy to a single site within 7 days prior to randomization
10. Corticosteroid therapy at a dose equivalent to dexamethasone > 4 mg/day within 21 days prior to randomization
11. Pregnant or lactating females
12. Major surgery within 21 days prior to randomization
13. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
14. Known human immunodeficiency virus infection
15. Active hepatitis B or C infection
16. Myocardial infarction within 4 months prior to randomization, New York Hear Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
17. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to randomization
18. Other malignancy, including myelodysplastic syndromes (MDS), within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
19. Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to randomization
20. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
21. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
22. Ongoing graft-vs-host disease
23. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization
24. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lenalidomide and Dexamethasone (Rd); Treatment was administered in cycles repeated every 28 days. Lenalidomide 25 mg was administered orally on days 1 to 21 and dexamethasone 40 mg was administered orally or IV on days 1, 8, 15, and 22.	Drug: Lenalidomide; 25 mg orally on days 1-21; Other Names: Revlimid; Drug: Dexamethasone; 40 mg orally or IV on days 1, 8, 15, 22
Experimental: Carfilzomib, Lenalidomide, and Dexamethasone (CRd); Treatment was administered in cycles every 28 days. Carfilzomib 20 mg/m² was administered intravenously (IV) on days 1 and 2 of cycle 1, escalating to 27 mg/m² on days 8, 9, 15, and 16 of cycle 1 and continuing on days 1, 2, 8, 9, 15, and 16 of cycle 2 through cycle 12 and then from cycle 13 through cycle 18, 27 mg/m² on days 1, 2, 15, and 16. Lenalidomide 25 mg was administered orally on days 1 to 21 from cycle 1 through cycle 18 and from cycle 19 and higher. Dexamethasone 40 mg was administered orally or IV on days 1, 8, 15, and 22 from cycle 1 through cycle 18 and from cycle 19 and higher.	Drug: Lenalidomide; 25 mg orally on days 1-21; Other Names: Revlimid; Drug: Dexamethasone; 40 mg orally or IV on days 1, 8, 15, 22; Drug: Carfilzomib; 20 mg/m², 27 mg/m² intravenously; Other Names: PR-171; Kyprolis®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	Kaplan-Meier estimate of median time from randomization to progressive disease (PD) or all-cause death. PD was assessed using International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). One or more conditions were required to meet PD: 2 consecutive rising serum or urine M-protein from central lab; documented new bone lesion(s) or soft tissue plasmacytoma(s) or increased size of existing bone lesion(s) or plasmacytoma(s); or confirmed hypercalcemia due solely to plasma cell proliferative disorder (local lab greater than 11.5 mg/dL on 2 separate occasions). Censoring conditions (censoring dates) were: no post-baseline disease assessment (DA) (randomization date); started non-protocol systemic anticancer treatment before PD or death (last DA date before such treatment); died or had PD after more than 1 missed DA (last DA date without PD before the first missed visit); or were alive and without documentation of PD, including lost to follow-up without PD (last DA date).	From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) was defined as the duration from randomization to death due to any cause. Participants who were still alive were censored at the date when the participant was last known to be alive or the data cutoff date, whichever occurred earlier.	From randomization through the data cutoff date of 28 April 2017 for the final analysis of overall survival; median follow up time was 67.1 months in each treatment group.
Overall Response Rate	Overall response rate is defined as the percentage of participants who achieved either a confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as their best response based on the Independent Review Committee (IRC) assessed response outcome. Response was determined using the International Myeloma Working Group - Uniform Response Criteria (IMWG-URC).	From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
Disease Control Rate	Disease control rate was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), or stable disease (SD) lasting ≥ 8 weeks according to International Myeloma Working Group - Uniform Response Criteria (IMWG-URC) (MR was determined using European Group for Blood and Marrow Transplantation criteria).	From randomization through the data cutoff date of 16 June 2014. Median follow-up time was approximately 31 months.
Duration of Response	Duration of response (DOR) was calculated for participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). Duration of response was defined as the time in months from the initial start of response (PR or better) to the earlier of documented progressive disease (PD) or death due to any cause. Participants who had not progressed or died were censored according to the censoring rules defined previously for PFS.	From randomization through the data cutoff date of 16 June 2014. Longest follow-up time was approximately 42 months.
Duration of Disease Control	Duration of disease control (DDC) was calculated for participants who achieved disease control. DDC was defined as the time in months from randomization to the earlier of documented progressive disease (PD) or death due to any cause. Participants who had not progressed or died were censored according to the censoring rules defined previously for PFS.	From randomization through the data cutoff date of 16 June 2014. Longest follow-up time was approximately 46 months.
Quality of Life Core Module (QLQ-C30) Global Health Status/Quality of Life Scores	Health-related quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer Quality of Life Core Module (QLQ-C30) questionnaire, a validated instrument in multiple myeloma patients. Scores range from 0 to 100, with higher scores indicating better health related quality of life.	Cycle 1 Day 1 (Baseline), Day 1 of Cycles 3, 6, 12, 18

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Dimopoulos M, Wang M, Maisnar V, Minarik J, Bensinger W, Mateos MV, Obreja M, Blaedel J, Moreau P. Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study. J Hematol Oncol. 2018 Apr 4;11(1):49. doi: 10.1186/s13045-018-0583-7.
• Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Spicka I, Masszi T, Hajek R, Rosinol L, Goranova-Marinova V, Mihaylov G, Maisnar V, Mateos MV, Wang M, Niesvizky R, Oriol A, Jakubowiak A, Minarik J, Palumbo A, Bensinger W, Kukreti V, Ben-Yehuda D, Stewart AK, Obreja M, Moreau P. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood. 2016 Sep 1;128(9):1174-80. doi: 10.1182/blood-2016-03-707596. Epub 2016 Jul 20.
• Dimopoulos MA, Stewart AK, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel D, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak A, San-Miguel J, Ludwig H, Ro S, Aggarwal S, Moreau P, Palumbo A. Carfilzomib-lenalidomide-dexamethasone vs lenalidomide-dexamethasone in relapsed multiple myeloma by previous treatment. Blood Cancer J. 2017 Apr 21;7(4):e554. doi: 10.1038/bcj.2017.31.
• Dimopoulos MA, Stewart AK, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel D, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak A, San-Miguel J, Ludwig H, Palumbo A, Obreja M, Aggarwal S, Moreau P. Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study. Br J Haematol. 2017 May;177(3):404-413. doi: 10.1111/bjh.14549. Epub 2017 Feb 17.
• Jakubowiak AJ, Campioni M, Benedict A, Houisse I, Tichy E, Giannopoulou A, Aggarwal SK, Barber BL, Panjabi S. Cost-effectiveness of adding carfilzomib to lenalidomide and dexamethasone in relapsed multiple myeloma from a US perspective. J Med Econ. 2016 Nov;19(11):1061-1074. doi: 10.1080/13696998.2016.1194278. Epub 2016 Jun 16.
• Stewart AK, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel DS, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Buchanan J, Cocks K, Yang X, Xing B, Zojwalla N, Tonda M, Moreau P, Palumbo A. Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma. J Clin Oncol. 2016 Nov 10;34(32):3921-3930. doi: 10.1200/JCO.2016.66.9648.
• 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.
• 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.
• 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.
• 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.
• 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.
• Siegel DS, Dimopoulos MA, Ludwig H, Facon T, Goldschmidt H, Jakubowiak A, San-Miguel J, Obreja M, Blaedel J, Stewart AK. Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2018 Mar 10;36(8):728-734. doi: 10.1200/JCO.2017.76.5032. Epub 2018 Jan 17.
• 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.
• Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A; ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. doi: 10.1056/NEJMoa1411321. Epub 2014 Dec 6.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2010
• Primary Completion (Actual): June 16, 2014
• Study Completion (Actual): December 5, 2017

Study Registration Dates

• First Submitted: March 2, 2010
• First Submitted That Met QC Criteria: March 2, 2010
• First Posted (Estimate): March 4, 2010

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide
• Other Study ID Numbers: PX-171-009