Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma

Multiple Myeloma Clinical Trial

— FIRST  

Official title:

A Phase III, Randomized, Open-label, 3-arm Study to Determine the Efficacy and Safety of Lenalidomide(REVLIMID) Plus Low-dose Dexamethasone When Given Until Progressive Disease or for 18 Four-week Cycles Versus the Combination of Melphalan, Prednisone, and Thalidomide Given for 12 Six-week Cycles in Patients With Previously Untreated Multiple Myeloma Who Are Either 65 Years of Age or Older or Not Candidates for Stem Cell Transplantation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00689936
• Other study ID #: CC-5013-MM-020
• Secondary ID: 2007-004823-39
• Status: Completed
• Phase: Phase 3
• Start date: August 21, 2008
• Est. completion date: July 14, 2016

Study information

• Verified date: November 2019
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the safety and efficacy of Lenalidomide plus low dose dexamethasone to that of the combination of melphalan, prednisone and thalidomide.

Description:

CC-5013-MM020/IFM 07-01 is a Phase III, multicenter, randomized, open-label, 3-arm study that will compare the efficacy and safety of two Lenalidomide plus low-dose dexamethasone regimens given for two different durations of time (i.e., until progressive disease [PD] or for up to a maximum of 18 four-week cycles) to that of MPT given for a maximum of 12 six-week cycles.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1623
• Est. completion date: July 14, 2016
• Est. primary completion date: July 14, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Must understand and voluntarily sign informed consent form

2. Age = 18 years at the time of signing consent

3. Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:

• MM diagnostic criteria (all 3 required):

• Monoclonal plasma cells in the bone marrow =10% and/or presence of a biopsy-proven plasmacytoma

• Monoclonal protein present in the serum and/or urine

• Myeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin <10 g/dl or 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis

AND have measurable disease by protein electrophoresis analyses as defined by the following:

• IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level = 1.0 g/dl or urine M-protein level = 200 mg/24 hours

• IgA multiple myeloma: Serum M-protein level = 0.5 g/dl or urine M-protein level = 200 mg/24 hours

• IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level = 1.0 g/dl or urine M-protein level = 200mg/24hours

• IgD multiple myeloma: Serum M-protein level = 0.05 g/dl or urine M-protein level = 200 mg/24 hours

• Light chain multiple myeloma: Serum M-protein level = 1.0 g/dl or urine M-protein level = 200 mg/24 hours

AND are at least 65 years of age or older or, if younger than 65 years of age, are not candidates for stem cell transplantation because:

• The patient declines to undergo stem cell transplantation or

• Stem cell transplantation is not available to the patient due to cost or other reasons

4. ECOG performance status of 0, 1, or 2

5. Able to adhere to the study visit schedule and other protocol requirements

6. Females of child-bearing potential (FCBP)^2:

1. Must agree to undergo two medically supervised pregnancy tests prior to starting study therapy with either Rd or MPT. The first pregnancy test will be performed within 10-14 days prior to the start of Rd or MPT and the second pregnancy test will be performed within 24 hours prior to the start of Rd or MPT. She must also agree to ongoing pregnancy testing during the course of the study and after the end of study therapy. This applies even if the patient practices complete and continued sexual abstinence.

2. Must commit to either continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy.

7. Male Patients:

1. Must agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy.

2. Must agree to not donate semen during study drug therapy and for a period after end of study drug therapy.

3. Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.

8. All patients must:

1. Have an understanding that the study drug could have a potential teratogenic risk.

2. Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.

3. Agree not to share study medication with another person. All FCBP and male patients must be counseled about pregnancy precautions and risks of fetal exposure.

Exclusion Criteria:

1. Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of randomization]).

2. Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, patient with unstable cardiac disease as defined by: Cardiac events such as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; patients with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.

3. Pregnant or lactating females.

4. Any of the following laboratory abnormalities:

• Absolute neutrophil count (ANC) < 1,000/µL (1.0 x 109/L)

• Untransfused platelet count < 50,000 cells/µL (50 x 10^9/L)

• Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)

5. Renal failure requiring hemodialysis or peritoneal dialysis.

6. Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for = 3 years. Exceptions include the following:

• Basal cell carcinoma of the skin

• Squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix

• Carcinoma in situ of the breast

• Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)

7. Patients who are unable or unwilling to undergo antithrombotic therapy.

8. Peripheral neuropathy of > grade 2 severity.

9. Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.

• 1 A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to be myeloma-related.

• 2 A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (i.e., amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Lenalidomide and low-dose dexamethasone
Lenalidomide - oral, 2.5mg, 5mg, 10mg, 15mg 20mg, or 25 mg capsules, given either days 1-21 of each 28 day cycles or given every other day for 21 days until documentation of PD. Dexamethasone - oral 4mg tablets for a total dose of 20mg or 40 mg given days 1,8,15 and 22 of each 28 day cycle up to disease progression
• Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles
lenalidomide - oral, 2.5mg, 5mg, 10mg, 15mg, 20 mg or 25 mg capsules given on days 1-21 of each 28 day cycle or every other day for 21 days for 18 cycles. Dexamethasone - oral 4mg tablets for a total dose of 20mg or 40 mg given days 1,8,15 and 22 of each 28 day cycle for 18 cycles
• Melphalan, Prednisone and Thalidomide
Melphalan - oral, 2mg tablets dosed at either 0.25mg/kg, 0.125 mg/kg, 0.20mg/kg or 0.10mg/kg on days 1-4 of each 42 day cycle up to 12 cycles Prednisone - oral, 5mg, 10mg, 20 mg and 50 mg tablets dosed at 2mg/kg daily days 1-4 of each 42 day cycle for up to 12 cycles Thalidomide - oral, 50mg, 100mg and 200 mg capsules dosed at either 100mg or 200 mg daily on days 1-41 of each 42 day cycle for up to 12 cycles

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinders Medical Centre	Bedford Park
Australia	Peter MacCallum Cancer Centre Divsion of Haematology Medical Oncology	E. Melbourne	Victoria
Australia	Western Hospital	Footscray	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Geelong Hospital	Geelong
Australia	Gosford Hospital	Gosford
Australia	Royal Brisbane and Women's Hospital	Herston
Australia	Cabrini Hospital	Malvern
Australia	The Royal Melbourne Hospital	Parkville
Australia	Royal Perth Hospital	Perth
Australia	Gold Coast Hospital	Southport
Australia	Royal North Shore Hospital	St Leonards
Australia	Westmead Hospital	Wentworthville
Australia	Border Medical Oncology	Wodonga
Australia	Wollongong Hospital	Wollongong
Australia	Princess Alexandra Hospital	Woolloongabba
Austria	Hospital Leoben	Leoben
Austria	General Hospital Linz	Linz
Austria	Hospital of Barmherzige Schwestern Linz	Linz
Austria	Hospital of Elisabethinen Linz	Linz
Austria	MM-015. Salzburger Landkliniken, St. Johanns-Spital, Universitätsklinik fur Innere Medizin III	Salzburg
Austria	Hospital St. Polten	St. Pölten
Austria	Hospital of the Barmherzigen Bruder Vienna	Vienna
Austria	MM-015. Medizinische Universität Wien	Vienna
Austria	MM-015.Wihelminenspital	Vienna
Austria	Hospital Wels	Wels
Austria	Hospital Wiener Neustadt	Wiener Neustadt
Belgium	ZNA Stuivenberg Centrumziekenhuis	Antwerpen
Belgium	Les Cliniques du Sud Luxembourg	Arlon
Belgium	AZ St-Jan Brugge Oostende AV	Brugge
Belgium	Jules Bordet Institut	Brussel
Belgium	AZ-VUB	Brussels
Belgium	Hopital Erasme	Brussels
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	UZ Gent	Gent
Belgium	Virga Jesse Ziekenhuis	Hasselt
Belgium	Universitair Ziekenhuis Leuven, Campus Gasthuisberg	Leuven
Belgium	H. Hartziekenhuis Roeselare-Menen vzw campus Wilgenstraat	Roeselare
Belgium	Cliniques Universitaires UCL de Mont-Godine	Yvoir
Canada	University of Calgary	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Hospital Charles LeMoyne	Greenfield Park	Quebec
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	British Columbia Cancer Agency	Kelowna	British Columbia
Canada	Hopital de la Cite-de-la-Sante	Laval	Quebec
Canada	Hotel-Dieu de Levis	Levis	Quebec
Canada	London Health Science Centre	London	Ontario
Canada	CHUM- Hopital Notre-Dame	Montreal	Quebec
Canada	Hopital du Sacre-Coeur de Montreal	Montreal	Quebec
Canada	Hospital Maisonneuve - Rosemont	Montreal	Quebec
Canada	McGill University	Montreal	Quebec
Canada	Sir Mortimer B. Davis - Jewish Genl	Montreal	Quebec
Canada	Royal Columbian Hospital	New Westminster	British Columbia
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	CHUQ - Hotel-Dieu de QuebecHematology - Oncology	Quebec
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	BC Cancer Agency - Fraser Valley Centre	Surrey	British Columbia
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Leukemia/BMT Program of BCDiv of Hem, Vancouver Gen Hosp	Vancouver	British Columbia
Canada	Vancouver Island Cancer Center	Victoria	British Columbia
China	Chaoyang Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	West China Hospital of Sichuan University	Chengdu
China	Ruijin Hospital Shanghai Jiaotong University	Shanghai
China	Blood Disease Hospital, Chinese Academy of Medical Science and Peking Union Medical College	Tianjin
France	Clinique Claude BernardOncologie	Albi
France	CHU Sud	Amiens
France	CHRU Hopital du bocage	Angers cedex 01
France	CH Argenteuil Victor Dupouy	Argenteuil
France	Centre Hospitalier de la cote basque	Bayonne
France	Centre Hospitalier	Blois cedex
France	Hopital Avicenne	Bobigny Cedex
France	Institut Bergonie Centre Regional de Lutte Contre Le Cancer de Bordeaux Et Sud Ouest	Bordeaux
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Hopital de Fleyriat	Bourg en Bresse cedex
France	Hopital Augustin Morvan	Brest cedex
France	CHU	Caen
France	Centre Francois Baclesse	Caen cedex 5
France	CH	Cannes Cedex
France	CH Rene Dubois	Cergy-Pontoise
France	Centre Hospitalier William Morey	Chalon/Saone Cedex
France	Hopital Antoine Beclere	Clamart
France	Hopital dinstruction des armees Percy	Clamart Cedex
France	Chu Estaing	Clermont Ferrand
France	CH Louis Pasteur	Colmar cedex
France	Hopital Henri Mondor	Creteil
France	CHRU Hopital du bocage	Dijon
France	Centre Hospitalier General	Dunkerque
France	Institut Prive de Cancerologie	Grenoble
France	CHRU	Grenoble cedex 09
France	Centre Hospitalier Departemental	La Roche -Sur-Yon cedex 9
France	CH	Le Chesnay Cedex
France	Hopital J MonodRhumato Nord	Le Havre
France	Kremlin Bicetre	Le Kremlin bicetre CDX
France	Centre Jean Bernard	Le Mans
France	Centre Hospitalier	Le Mans cedex
France	GH de Institut Catholique St Vincent	Lille
France	CHRU-Hopital Claude Huriez	Lille cedex
France	CH - Hôpital Dupuytren	Limoges Cedex 1
France	Centre Hospitalier de Valence	Lyon
France	Centre Leon Berard	Lyon
France	CHU Hopital Edouard Herriot	Lyon cedex
France	Institut Paoli-Calmettes	Marseille Cedex 9
France	Hopital de Mercy	METZ cedex 3
France	Clinique Pont de chaume Oncologie et Radiotherapie	Montauban cedex
France	CHU Montpellier - Hôpital Lapeyronie	Montpellier Cedex 5
France	Hopital Emile Muller	Mulhouse
France	CHRU - Hotel Dieu	Nantes
France	Centre Antoine Lacassagne Oncologie medicale et Hematologie	Nice cedex 1
France	Hopital de lArchet 1	Nice cedex 3
France	CH La Source	Orleans
France	CHU Hôpital St-Antoine	Paris
France	Hopital Necker	Paris
France	Hopital Saint Louis	Paris
France	Hopital Cochin	Paris Cedex 14
France	CHRU - Hopital du Haut Leveque	Pessac
France	CU CHU Clemenceau	Poitiers cedex
France	CHU Reims - Hôpital Maison Blanche	Reims
France	Hopital R. Debre	Reims cedex
France	CHRU Hôpital de Pontchaillou	Rennes Cedex
France	CHRU Hopital sud Medecine Interne	Rennes cedex 02
France	CHG Rodez	Rodez
France	Centre Henri Becquerel	Rouen cedex
France	Centre Rene Huguenin	Saint Cloud
France	Institut de Cancerologie de Loire	St Priest en Jarez
France	Centre Hospitalier Yves Le Foll	St-Brieuc cedex 1
France	CHRU Hôpital de Hautepierre	Strasbourg
France	CHRU Hopital Purpan	Toulouse cedex 9
France	CHRU Hopital Trousseau	Tours
France	CHRU Hopital Bretonneau	Tours cedex
France	CHRU Hôpitaux de Brabois	Vandoeuvre Cedex
France	CH P. Chubert	Vannes cedex
France	Institut Gustave Roussy	Villejuif
Germany	Medizinische Kinik und Poliklinik I	Dresden
Germany	Universitaetsklinikum Dusseldorf Klinik fuer Haematologie	Dusseldorf
Germany	Universitatsklinikum Essen-	Essen
Germany	Staedtische Kliniken Frankfurt am Main Hochst	Frankfurt am Main
Germany	Universitatsklinikum Giessen	Giessen
Germany	Ernst-Moritz-Arndt-Universität Greifswald	Greifswald
Germany	Askepios Klinik St. Georg	Hamburg
Germany	Universitatsklinikum Jena	Jena
Germany	Medizinische Klinik und Poliklinik II	Leipzig
Germany	Universitatsklinikum schleswig-Holstein	Lübeck
Germany	Poliklinik A	Muenster
Germany	Klinikum der Johann-Wolfgang-Goethe-Universtat	München
Germany	Medizinische Klinik III Klinikum der Universität München-Großhadern	München
Germany	Medizinische Fakultat der Universitat Rostock	Rostock
Germany	Zentrum F. Innere Medizin II Robert- Bosch-Krankenhaus GmBH	Stuttgart
Germany	Medizinische Klinik - Abteilung II	Tübingen
Germany	Klinik fur Innere Medizin III	Ulm
Greece	Alexandra Hospital, University of Athens	Athens
Greece	Attiko Hospital of Athens	Athens
Greece	Evangelismos Hospital of Athens	Athens
Greece	University of Athens	Athens
Greece	Metaxa Hospital Peiraias	Piraeus
Greece	Theagenio Anticancer Hospital of Thessaloniki	Thessaloniki
Ireland	Adelaide and Meath Hospital	Dublin
Ireland	Mater Misercordiae Hospital	Dublin
Ireland	University Hospital Galway	Galway
Italy	Policlinico S. Orsola	Bologna
Italy	Oncologia Medica, Università della Magna Grecia	Catanzaro
Italy	Clinica Ematologica, A.O.U. San Martino di Genova	Genova
Italy	Ematologia ed Immunologia, Azienda Ospedaliera Vito Fazzi di Lecce	Lecce
Italy	Unità Operativa di Oncoematologia, Ospedale di Matera	Matera
Italy	Istituto Europeo di Oncologia - IEO	Milano
Italy	Presidio Ospedaliero A. Perrino	Milano
Italy	U.O. di Ematologia e Trapianto di Midollo Osseo	Milano
Italy	Policlinico di Modena	Modena
Italy	Oncoematologia, Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Casa di Cura La Maddalena, Divisione di Ematologia	Palermo
Italy	Policlinico San Matteo Universita Di Pavia	Pavia 2
Italy	Ospedale Civile	Piacenza
Italy	A.O. Universitaria Ospedale S.Chiara Dip.Oncologia, Div. Ematologia	Pisa
Italy	Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Istituto Nazionale Tumori Regina Elena, Struttura Complessa Ematologia ed Unita di Cellule Staminali	Roma
Italy	Azienda Policlinico Umberto I, Universita La Sapienzadi Roma	Rome
Italy	Ospedale Molinette	Torino
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Daegu Catholic University Medical Center 3056-6	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejon
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Hwasun Chonnam National University Hospital	Hwasun-goon
Korea, Republic of	Gachon University Gil Hospital	Incheon
Korea, Republic of	Chonbuk National University Hospital 42	Jeonju
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Severance Hospital	Seongsanno
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea Seoul - Saint Mary's Hospital	Seoul
New Zealand	Auckland City Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Wellington Hospital	Newtown
Portugal	Hospital de Sao Marcos	Braga
Portugal	Hospitais da Universidade de Coimbra	Coimbra
Portugal	Hospital de Santa Maria	Lisboa
Portugal	Instituto Portugues de Oncologia de Lisboa	Lisboa
Portugal	Hospital de Santo Antonio- Porto	Porto
Portugal	Instituto Português de Oncologia Porto	Porto
Spain	Hospital Universitari Germans Trias i Pujol	Badalona (Barcelona)
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Instituto Catalan de Oncologia-Hospital Duran	Barcelona
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital Univ. Josep Trueta	Girona
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Clinico Virgen de la Victoria	Málaga
Spain	Hospital General Universitario Morales Messeguer	Murcia
Spain	Hospital Son Llatzer	Palma de Mallorca
Spain	Clinica Universitaria de Navarra,	Pamplona
Spain	Hospital Sant Pau	Reus
Spain	Hospital de Donosti	San Sebastian
Spain	Hospital Universtario Marques de Valdecilla	Santander
Spain	Hospital Clinico Santiago de Compostela	Santiago de Compostela
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hosptial La Fe	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Miguel Servet	Zaragoza
Sweden	Linkoping University Hospital	Linkoping
Sweden	Karolinska University Hospital Huddinge	Stockholm
Sweden	Karolinska University HospitalSolna	Stockholm
Sweden	St. Görans Hospital	Stockholm
Switzerland	Abteilung Onkologie Haematologie des Kantonsspitals Aarau	Aarau
Switzerland	UniversitatsSpital Basel	Basel
Switzerland	Inselsspital Bern	Berne
Switzerland	Kantonsspital Graubunden	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois CHUV	Lausanne
Switzerland	Kantonsspital Munsterlingen	Münsterlingen (TG)
Switzerland	Kantonsspital Winterthur	Winterthur
Taiwan	China Medical University Hospital	Taichung City
Taiwan	Veteran General Hospital - Taipei	Taipei
Taiwan	National Taiwan University Hospital	Tapei
United Kingdom	Gwynedd Hospital	Bangor
United Kingdom	Royal United Hospital	Bath
United Kingdom	Belfast City Hospital Haematology Department	Belfast Northern Ireland
United Kingdom	Birminghman QE	Birmingham West Midlands
United Kingdom	Royal Bournemouth Hosp	Bournemouth Dorset
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	University Hospital of Wales - Cardiff	Cardiff
United Kingdom	The Beatson West of Scotland Centre	Glasgow
United Kingdom	Dept of Haematology St Bartholomews Hospital	London
United Kingdom	Guy's and St Thomas' Hospital - London	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Churchhill Hospital	Oxford
United Kingdom	Derriford Hospital	Plymouth Crownhill Devon
United Kingdom	Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Trust	Sheffield
United Kingdom	Pinderfields General Hospital	West Yorkshire
United Kingdom	New Cross Hospital- Wolverhampton	Wolverhampton
United States	St. Luke's Hospital and Health Network	Allentown	Pennsylvania
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Billings Clinic	Billings	Montana
United States	University of AL Birmingham	Birmingham	Alabama
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Southern Illinois Hematology Oncology	Centralia	Illinois
United States	John H Stroger Hospital of Cook County	Chicago	Illinois
United States	Orchard Healthcare Research, Inc.	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	The Cancer Center	Collierville	Tennessee
United States	Dakota Cancer Institute	Fargo	North Dakota
United States	Gainesville Heme Oncology Associates	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Ingalls Cancer Institute	Harvey	Illinois
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Arena Oncology Associates, PC	Lake Success	New York
United States	Cedar Sinai Medical Center Dept of Medicine	Los Angeles	California
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	Integrated Community Oncology Network	Orange Park	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Kaiser Permanente Northwest Oncology Hematology	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Gulf Coast Oncology	Saint Petersburg	Florida
United States	University of California, San Francisco- California	San Francisco	California
United States	Maine Center for Cancer Medicine Blood Disorders	Scarborough	Maine
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	Stanford University Stanford	Stanford	California
United States	Palm Beach Cancer Institute, LLC	West Palm Beach	Florida
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  France,  Germany,  Greece,  Ireland,  Italy,  Korea, Republic of,  New Zealand,  Portugal,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

References & Publications (13)

Ailawadhi S, DerSarkissian M, Duh MS, Lafeuille MH, Posner G, Ralston S, Zagadailov E, Ba-Mancini A, Rifkin R. Cost Offsets in the Treatment Journeys of Patients With Relapsed/Refractory Multiple Myeloma. Clin Ther. 2019 Mar;41(3):477-493.e7. doi: 10.1016/j.clinthera.2019.01.009. Epub 2019 Feb 14. — View Citation

Ailawadhi S, Jacobus S, Sexton R, Stewart AK, Dispenzieri A, Hussein MA, Zonder JA, Crowley J, Hoering A, Barlogie B, Orlowski RZ, Rajkumar SV. Disease and outcome disparities in multiple myeloma: exploring the role of race/ethnicity in the Cooperative Group clinical trials. Blood Cancer J. 2018 Jul 6;8(7):67. doi: 10.1038/s41408-018-0102-7. — View Citation

Bahlis NJ, Corso A, Mugge LO, Shen ZX, Desjardins P, Stoppa AM, Decaux O, de Revel T, Granell M, Marit G, Nahi H, Demuynck H, Huang SY, Basu S, Guthrie TH, Ervin-Haynes A, Marek J, Chen G, Facon T. Benefit of continuous treatment for responders with newly — View Citation

Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis N, Banos A, Tiab M, Delforge M, Cavenagh J, Geraldes C, Lee JJ, Chen C, Oriol A, de la Rubia J, Qiu L, White DJ, Binder D, Anderson K, Fermand JP, Moreau P, Attal M, Knight R, Chen G, Van Oostendorp J, Jacques C, Ervin-Haynes A, Avet-Loiseau H, Hulin C, Facon T; FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014 Sep 4;371(10):906-17. doi: 10.1056/NEJMoa1402551. — View Citation

Delforge M, Minuk L, Eisenmann JC, Arnulf B, Canepa L, Fragasso A, Leyvraz S, Langer C, Ezaydi Y, Vogl DT, Giraldo-Castellano P, Yoon SS, Zarnitsky C, Escoffre-Barbe M, Lemieux B, Song K, Bahlis NJ, Guo S, Monzini MS, Ervin-Haynes A, Houck V, Facon T. Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide. Haematologica. 2015 Jun;100(6):826-33. doi: 10.3324/haematol.2014.120121. Epub 2015 Mar 13. — View Citation

Dimopoulos MA, Cheung MC, Roussel M, Liu T, Gamberi B, Kolb B, Derigs HG, Eom H, Belhadj K, Lenain P, Van der Jagt R, Rigaudeau S, Dib M, Hall R, Jardel H, Jaccard A, Tosikyan A, Karlin L, Bensinger W, Schots R, Leupin N, Chen G, Marek J, Ervin-Haynes A, Facon T. Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma. Haematologica. 2016 Mar;101(3):363-70. doi: 10.3324/haematol.2015.133629. Epub 2015 Dec 11. — View Citation

Dumontet C, Hulin C, Dimopoulos MA, Belch A, Dispenzieri A, Ludwig H, Rodon P, Van Droogenbroeck J, Qiu L, Cavo M, Van de Velde A, Lahuerta JJ, Allangba O, Lee JH, Boyle E, Perrot A, Moreau P, Manier S, Attal M, Roussel M, Mohty M, Mary JY, Civet A, Costa B, Tinel A, Gaston-Mathé Y, Facon T. A predictive model for risk of early grade = 3 infection in patients with multiple myeloma not eligible for transplant: analysis of the FIRST trial. Leukemia. 2018 Jun;32(6):1404-1413. doi: 10.1038/s41375-018-0133-x. Epub 2018 Apr 26. — View Citation

Facon T, Dimopoulos MA, Dispenzieri A, Catalano JV, Belch A, Cavo M, Pinto A, Weisel K, Ludwig H, Bahlis NJ, Banos A, Tiab M, Delforge M, Cavenagh JD, Geraldes C, Lee JJ, Chen C, Oriol A, De La Rubia J, White D, Binder D, Lu J, Anderson KC, Moreau P, Attal M, Perrot A, Arnulf B, Qiu L, Roussel M, Boyle E, Manier S, Mohty M, Avet-Loiseau H, Leleu X, Ervin-Haynes A, Chen G, Houck V, Benboubker L, Hulin C. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood. 2018 Jan 18;131(3):301-310. doi: 10.1182/blood-2017-07-795047. Epub 2017 Nov 17. — View Citation

Hulin C, Belch A, Shustik C, Petrucci MT, Dührsen U, Lu J, Song K, Rodon P, Pégourié B, Garderet L, Hunter H, Azais I, Eek R, Gisslinger H, Macro M, Dakhil S, Goncalves C, LeBlanc R, Romeril K, Royer B, Doyen C, Leleu X, Offner F, Leupin N, Houck V, Chen G, Ervin-Haynes A, Dimopoulos MA, Facon T. Updated Outcomes and Impact of Age With Lenalidomide and Low-Dose Dexamethasone or Melphalan, Prednisone, and Thalidomide in the Randomized, Phase III FIRST Trial. J Clin Oncol. 2016 Oct 20;34(30):3609-3617. doi: 10.1200/JCO.2016.66.7295. — View Citation

Jain T, Sonbol MB, Firwana B, Kolla KR, Almader-Douglas D, Palmer J, Fonseca R. High-Dose Chemotherapy with Early Autologous Stem Cell Transplantation Compared to Standard Dose Chemotherapy or Delayed Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant. 2019 Feb;25(2):239-247. doi: 10.1016/j.bbmt.2018.09.021. Epub 2018 Sep 20. — View Citation

Lu J, Lee JH, Huang SY, Qiu L, Lee JJ, Liu T, Yoon SS, Kim K, Shen ZX, Eom HS, Chen WM, Min CK, Kim HJ, Lee JO, Kwak JY, Yiu W, Chen G, Ervin-Haynes A, Hulin C, Facon T. Continuous treatment with lenalidomide and low-dose dexamethasone in transplant-ineli — View Citation

Pegourie B, Karlin L, Benboubker L, Orsini-Piocelle F, Tiab M, Auger-Quittet S, Rodon P, Royer B, Leleu X, Bareau B, Cliquennois M, Fuzibet JG, Voog E, Belhadj-Merzoug K, Decaux O, Rey P, Slama B, Leyronnas C, Zarnitsky C, Boyle E, Bosson JL, Pernod G; IFM Group. Apixaban for the prevention of thromboembolism in immunomodulatory-treated myeloma patients: Myelaxat, a phase 2 pilot study. Am J Hematol. 2019 Jun;94(6):635-640. doi: 10.1002/ajh.25459. Epub 2019 Apr 1. — View Citation

Vogl DT, Delforge M, Song K, Guo S, Gibson CJ, Ervin-Haynes A, Facon T. Long-term health-related quality of life in transplant-ineligible patients with newly diagnosed multiple myeloma receiving lenalidomide and dexamethasone. Leuk Lymphoma. 2018 Feb;59(2):398-405. doi: 10.1080/10428194.2017.1334125. Epub 2017 Jun 22. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC)	PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).	From date of randomization until the data cut-off date of 24 May 2013. Median follow-up time for all participants was 17.1 months.
Primary	Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis	PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).	From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 17.7 months
Secondary	Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS)	Overall survival was defined as the time between randomization and death. Participants, who died, regardless of the cause of death, were considered to have had an event. All participants who were lost to follow-up prior to the end of the trial or who were withdrawn from the trial were censored at the time of last contact. Participants who were still being treated were censored at the last available date the participant was known to be alive.	From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 48.3 months
Secondary	Percentage of Participants With an Objective Response Based on IRAC Review	Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined as: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis	Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC	Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median follow-up for responders was 20.1 months
Secondary	Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis	Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first.	Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median follow-up for responders was 19.9 months
Secondary	Time to First Response Based on the Review by the IRAC	The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Time to First Response Based on the Investigator Assessment at the Time of Final Analysis	The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria assessed by the investigator.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm.
Secondary	Kaplan Meier Estimates of Time to Treatment Failure (TTF)	TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by IRAC based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.	From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 16.1 months.
Secondary	Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis	TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by the investigators assessment based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.	From date of randomization until the data cut-off date of 21 January 2016; median follow up for all participants was 16.1 months.
Secondary	Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT)	Time to second-line anti-myeloma therapy was defined as time from randomization to the start of another non-protocol anti-myeloma therapy.	From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 23.0 months
Secondary	Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis	Time to second-line anti-myeloma therapy is defined as time from randomization to the start of another non-protocol anti-myeloma therapy. Those who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.	From date of randomization until the data cut-off of date 21 January 2016; median follow-up for all participants was 23.0 months
Secondary	Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis	Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.	Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review.	Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review	Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review	Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review	Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and =5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or =90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is =50% reduction of serum M-Protein and reduction in urinary M-protein by =90% or to <200 mg/24 hours. If present at baseline a =50% reduction in size of soft tissue plasmacytomas.	Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Cycle 1 Day 1, (Baseline) then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Fatigue Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation
Secondary	Change From Baseline in the EORTC QLQ-C30 Pain Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Insomnia Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Scale is scored between 0 and 100, with a high score indicating a higher level of appetite loss. Negative change from Baseline values indicate improvement in appetite and positive values indicate worsening of appetite.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Constipation Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale is scored between 0 and 100, with a high score indicating a higher level of constipation. Negative change from Baseline values indicate improvement in constipation and positive values indicate worsening of constipation.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100, with a high score indicating a higher level of diarrhea. Negative change from Baseline values indicate improvement in diarrhea and positive values indicate worsening of diarrhea.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain	The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Difficulties Scale is scored between 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicate improvement in financial difficulties and positive values indicate worsening of financial difficulties.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score indicates more severe disease symptom(s).	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the body image scale, a higher score indicates a better body image.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score	EQ-5D is a self-administered questionnaire that assesses health-related quality of life. The EQ-5D descriptive health profile comprises five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 3 levels of response: No problem (1), some problems (2), and extreme problems (3). A unique EQ-5D health state is defined by combining one level from each of the five dimensions into a single utility index score. EQ-5D index values range from -0.59 to 1.00 where higher EQ-5D scores represent better health status. A positive change from baseline score indicates improvement in health status and better health state.	Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Secondary	Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year	HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of inpatient hospitalizations per patient year was calculated as the total number of hospitalizations divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.	Day 1 (randomization) up to last visit completed 25 July 2016
Secondary	Number of Participants With Adverse Events (AEs) During the Active Treatment Phase	A TEAE is any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event.	From first dose of study drug through 28 days following the discontinuation visit from active treatment phase; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase	Renal function was assessed for participants from baseline to the most extreme value in creatinine clearance calculated using the Cockcroft-Gault estimation.	Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase	Neutrophil counts was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.	Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase	Hemoglobin was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.	Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase.	Improvement in platelets was assessed for participants from baseline grade to most extreme severity grade using the NCI CTCAE v 3.0 grading scale.	Randomization to end of treatment or the data cut off of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Secondary	Improvement of Infection Rate by Observing the Historical Data Compared to the Clinical Data Base	Improvement of infection rate by observing historical data compared to the data within clinical database as not analyzed.	From randomization to 24 May 2013

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