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

Relapsed Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01080391
• Other study ID #: PX-171-009
• Status: Completed
• Phase: Phase 3
• Start date: July 14, 2010
• Est. completion date: December 5, 2017

Study information

• Verified date: September 2022
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 792
• Est. completion date: December 5, 2017
• Est. primary completion date: June 16, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed Multiple Myeloma

Intervention

Drug:
• Dexamethasone
40 mg orally or IV on days 1, 8, 15, 22
• Lenalidomide
25 mg orally on days 1-21
• Carfilzomib
20 mg/m², 27 mg/m² intravenously

Locations

Country	Name	City	State
Austria	Medizinische Universitat Wien	Wien
Austria	Wilhelminspital der Stadt Wien, Zentrum fur Onkologie und Hamatologie	Wien
Belgium	Ziekenhuisnetwerk Antwerpen - AZ Stuivenberg	Antwerpen
Belgium	AZ Sint-Jan AV	Brugge
Belgium	UZ Brussel	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Institut Jules Bordet	Bruxelles
Belgium	UZ Leuven	Leuven
Bulgaria	University Multiprofile Hospital for Active Treatment, "Dr. Georgi Stranski"	Pleven
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Georgi"	Plovdiv
Bulgaria	Military Medical Academy Multiprofile Hospital for Active Treatment	Sofia
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment "Sveta Marina"	Varna
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	University of Alberta, Cross Cancer Institute	Edmonton	Alberta
Canada	McGill University Health Center, Royal Victoria Hospital	Montreal	Quebec
Canada	Sir Mortimer B. Davis - Jewish General Hospital	Montreal	Quebec
Canada	General Hospital, Health Sciences Centre	St John's	Newfoundland and Labrador
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Czechia	University Hospital Brno, Department of Internal Medicine - Hematooncology	Brno
Czechia	University Hospital Hradec Kralove	Hradec Kralove
Czechia	University Hospital Olomouc	Olomouc
Czechia	University Hospital Kralovske Vinohrady - Prague	Praha 10
Czechia	General University Hospital Prague	Praha 2
France	Hospital Antoine Beclere	Clamart
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans
France	Hopital Claude Huriez	Lille
France	CH de Mulhouse, Hopital Emile Muller	Mulhouse
France	CHU Nantes Hotel Dieu	Nantes
France	Groupe Hospitalier Necker - Enfants Malades	Paris
France	Hopital Saint-Antoine	Paris
France	Cancer Institut Universitaire de Toulouse-Oncopole (iUCT)	Toulouse
France	Hopitaux de Brabois	Vandoeuvre-Les-Nancy
Germany	University of Dusseldorf	Dusseldorf
Germany	Krankenhaus Nordwest	Frankfurt am Main
Germany	University of Hamburg-Eppendorf	Hamburg
Germany	Universitat Heidelberg	Heidelberg
Germany	Stiftungsklinikum Mittelrhein	Koblenz
Germany	LMU Klinikum der Universitat	Munchen
Germany	Universitatsklinikum Munster	Munster
Germany	Universitatsklinikum Wurzburg	Wurzburg
Greece	Alexandra Hospital	Athens
Greece	University General Hospital of Patras	Patras
Hungary	St. Istvan and St. Laszlo Hospital of Budapest	Budapest
Hungary	University of Debrecen, Medical and Health Science Center	Debrecen
Hungary	Petz Aladar County Teaching Hospital	Gyor
Hungary	Bekes County Pandy Kalman Hospital	Gyula
Hungary	Kaposi Mor County Teaching Hospital	Kaposvar
Hungary	University of Pecs	Pecs
Hungary	University of Szeged, Albert Szent-Gyorgi Clinical Center	Szeged
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center, Ein Kerem	Jerusalem
Israel	Western Gailee Hospital - Nahariya	Nahariya
Israel	Rabin Medical Center	Petach Tikva
Israel	The Chaim Sheba Medical Center	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Italy	Azienda Ospedallera Niguarda Ca Granda	Milano
Italy	Azienda Ospedllero Maggiore della Carita	Novara
Italy	Azienda Ospedaliera Pisana Ospendale Santa Chiara - Main	Pisa
Italy	Ospedale S. Eugenio	Roma
Italy	Azienda Ospedaliera Citta della Salute e della Scienza di Torino	Torino
Netherlands	Erasmus MC, Department of Haematology	Rotterdam
Poland	University Clinical Centre, Department of Hematologii Transplantologii	Gdansk
Poland	Samodzielny Publ. Szp. Wojewodzki w Gorzow Wlkp.	Gorzow Wielkopolski
Poland	Independent Public Teaching Hospital of Medical University of Silesia in Katowice	Katowice
Poland	Nicolaus Copernicus Memorial Provincial Specialist Hospital in Lodz	Lodz
Poland	Szpital Wojewwodzki im. dr Ludwika Rydygiera w Suwalkach	Suwalki
Poland	Nicolaus Copernicus Municipal Specialist Hospital	Torun
Poland	Maria Sklodowska-Curie Institute of Oncology	Warszawa
Poland	Zamojski Non-Public Hospital	Zamosc
Romania	Bucharest University Emergency Hospital	Bucharest
Romania	Coltea Clinical Hospital	Bucharest
Romania	Fundeni Clinical Institute, "Stefan Berceanu" Center for Hematology and Bone Marrow Transplantation	Bucharest
Romania	Regional Institute of Iasi	Iasi
Russian Federation	First Republican Clinical Hospital under the Ministry of Healthcare of the Republic of Udmurtia	Izhevsk
Russian Federation	Federal State Budget Institution: Hematology Research Center under MoH	Moscow
Russian Federation	Federal State Budgetary Scientific Institution: N.N. Blokhin Russian Cancer Research Center	Moscow
Russian Federation	Moscow State Medical Institution Municipal City Clinical Hospital n.a. S.P. Botkin	Moscow
Russian Federation	Federal State Budget Institute: Federal Almalov Medical Research Centre under Ministry of Healthcare	St. Petersburg
Russian Federation	FSBI: Russian Research Institute of Hematology and Blood Transfusion under the Ferderal Agency for M&B	St. Petersburg
Russian Federation	SHEI: First St. Petersburg State Medical University N.a.I.P Pavlov under MoH, Clinic of Bone Marrow Transplant	St. Petersburg
Russian Federation	State Higher Educational Institution: St Petersburg State Medical University n.a.I.P Pavlov	St. Petersburg
Russian Federation	State Medical Institution Komi Republican Oncological Center	Syktyvkar	Komi Republic
Serbia	Clinical Center of Serbia, Clinic of Hematology	Belgrade
Serbia	Clinical Hospital Center Bezanijska Kosa	Belgrade
Serbia	Military Medical Academy, Clinic of Hematology	Belgrade
Serbia	Clinical Center Nis, Clinic of Hematology	Nis
Serbia	Clinical Center of Vojvodina, Clinic of Hematology	Novi Sad
Spain	Hospital Universitario Germans Trias i Pujol	Badalona
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Donostia	San Sebastian
Spain	Hospital Universitario y Politeecnico La Fe	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg
Sweden	Karolinska Universitetsjukhuset i Huddinge	Stockholm
Sweden	Karolinska Universitetssjukhuset Solna, Hematologiskt Centrum	Stockholm
United Kingdom	Royal Free Hampstead	London
United Kingdom	St. Bartholomew's Hospital	London
United Kingdom	St. Georges Hospital	London
United Kingdom	Nottingham University Hospitals (City Campus)	Nottingham
United Kingdom	Royal Marsden Hospital	Sutton
United Kingdom	The Royal Wolverhampton Hospital NHS Trust	Wolverhampton
United States	The Don & Sybil Harrington Cancer Center	Amarillo	Texas
United States	The University of Michigan - Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Providence St. Joseph Medical Center	Burbank	California
United States	Associates in Oncology and Hematology	Chattanooga	Tennessee
United States	Rush University Medical Center	Chicago	Illinois
United States	Baylor Sammons Cancer Center	Dallas	Texas
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Cancer and Blood Disease Center	Lecanto	Florida
United States	Froedtert & Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Clinical Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	St. Jude Hospital Yorba Linda dba; St. Joseph Heritage Healthcare	Santa Rosa	California
United States	Mayo Clinic	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Scott and White Memorial Hospital	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Netherlands,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Sweden,  United Kingdom, 

References & Publications (13)

Avet-Loiseau H, Fonseca R, Siegel D, Dimopoulos MA, Špicka I, Masszi T, Hájek R, Rosiñol 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. — View Citation

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. Review. — View Citation

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. — View Citation

Dimopoulos MA, Stewart AK, Masszi T, Špicka I, Oriol A, Hájek R, Rosiñol 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. — View Citation

Dimopoulos MA, Stewart AK, Masszi T, Špicka I, Oriol A, Hájek R, Rosiñol 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. — 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

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, Campioni M, Benedict Á, 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. Epub 2016 Jun 16. — 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

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

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. — View Citation

Stewart AK, Dimopoulos MA, Masszi T, Špicka I, Oriol A, Hájek R, Rosiñol 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. — 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 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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

External Links

•   AmgenTrials clinical trials website