UPFRONT: Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone

Sponsor

Millennium Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00507416

Collaborator

(none)

502

Enrollment

235

Locations

Arms

Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, open label, multicenter clinical trial to compare the efficacy and safety of Velcade (bortezomib) and dexamethasone versus Velcade, thalidomide, and dexamethasone versus Velcade, melphalan, and prednisone in patients with previously untreated multiple myeloma not considered candidates for high-dose chemotherapy and autologous stem cell transplantation.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Bortezomib Drug: Dexamethasone Drug: Melphalan Drug: Prednisone Drug: Thalidomide	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

502 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized Phase 3b Study of Three Treatment Regimens in Subjects With Previously Untreated Multiple Myeloma Who Are Not Considered Candidates for High-Dose Chemotherapy and Autologous Stem Cell Transplantation: VELCADE, Thalidomide, and Dexamethasone Versus VELCADE and Dexamethasone Versus VELCADE, Melphalan, and Prednisone

Study Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bortezomib and Dexamethasone (VD) Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Drug: Bortezomib Bortezomib bolus intravenous (IV) injection Other Names: Velcade Drug: Dexamethasone Dexamethasone for oral administration
Experimental: Bortezomib, Thalidomide, and Dexamethasone (VTD) Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance) .	Drug: Bortezomib Bortezomib bolus intravenous (IV) injection Other Names: Velcade Drug: Dexamethasone Dexamethasone for oral administration Drug: Thalidomide Thalidomide for oral administration
Experimental: Bortezomib, Melphalan and Prednisone (VMP) Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Drug: Bortezomib Bortezomib bolus intravenous (IV) injection Other Names: Velcade Drug: Melphalan Melphalan for oral administration Drug: Prednisone Prednisone for oral administration

Arm

Intervention/Treatment

Experimental: Bortezomib and Dexamethasone (VD)

Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).

Drug: Bortezomib

Bortezomib bolus intravenous (IV) injection

Other Names:

Velcade

Drug: Dexamethasone

Dexamethasone for oral administration

Experimental: Bortezomib, Thalidomide, and Dexamethasone (VTD)

Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance) .

Drug: Bortezomib

Bortezomib bolus intravenous (IV) injection

Other Names:

Velcade

Drug: Dexamethasone

Dexamethasone for oral administration

Drug: Thalidomide

Thalidomide for oral administration

Experimental: Bortezomib, Melphalan and Prednisone (VMP)

Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).

Drug: Bortezomib

Bortezomib bolus intravenous (IV) injection

Other Names:

Velcade

Drug: Melphalan

Melphalan for oral administration

Drug: Prednisone

Prednisone for oral administration

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [From randomization until disease progression. Median follow-up time was 43 months.]
PFS is defined as the time from randomization to disease progression or death, whichever occurs first. Participants who did not progress and were still alive at the cut-off date were censored at the date of last contact. Response was assessed by the Investigator using the International Myeloma Working Group (IMWG) uniform response criteria. Progressive disease requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl) Urine M-component (absolute increase ≥ 200 mg/24 hours) In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl) Bone marrow plasma cell percentage (absolute % ≥ 10%) Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease

Secondary Outcome Measures

Percentage of Participants With an Overall Response [Response assessed every other cycle for up to 13 cycles (49 weeks).]
Overall response defined as a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR), assessed by the Investigator using the IMWG uniform response criteria. CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours (h). PR requires 1 of the following: ≥50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to <200 mg/24 h, or If M-protein not measurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels, or If FLC not measurable, a ≥ 50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was ≥30%. If present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.
Percentage of Participants With a Complete Response [Response assessed every other cycle, for up to 13 cycles (49 weeks).]
Participants with a best overall response of complete response, defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. Response was assessed by the Investigator using the IMWG uniform response criteria.
Percentage of Participants With a Complete Response or a Very Good Partial Response [Response assessed every other cycle for up to 13 cycles (49 weeks).]
Complete response is defined by negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. Very good partial response is defined by serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. Response was assessed by the Investigator using the IMWG uniform response criteria.
Duration of Response [From first documented response until disease progression. Median follow-up time was 43 months.]
Duration of response is defined in participants with an overall response as the time between first documentation of response and disease progression. Responders without disease progression were censored at the last clinical assessment of response.
Overall Survival [From randomization until death. Median follow-up time was 43 months.]
Overall survival is defined as the time between randomization and death. Participants still alive at the cutoff date or lost to follow-up were censored at the date of last contact.
Time to Alternative Therapy [From randomization until alternative therapy. Median follow-up time was 43 months.]
Time to alternative therapy is defined as the time between randomization and alternative therapy. Participants who did not receive alternative therapy were censored at the time of last contact.
Change From Baseline in EORTC QLQ-C30 - Global Health Status [Baseline and Day 1 of Cycles 3, 5, 7, 9, 11 and 13]
The European Organisation 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, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female 18 years of age or older
Not a candidate for high-dose chemotherapy and stem cell transplantation (HDT/SCT) due to age, presence of important comorbid condition(s) likely to have a negative impact on tolerability of HDT-SCT, or subject preference.
A Karnofsky Performance Status score of ≥50%
Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage.
Asymptomatic multiple myeloma-related organ or tissue damage can include presence of an asymptomatic lytic bone lesion or plasmacytoma, the presence of anemia (hemoglobin <10 g/dL), renal function impairment (serum creatinine > upper limit of normal [ULN]) or hypercalcemia (serum calcium >ULN).
Must have measurable disease requiring systemic therapy. Measurable disease is defined by at least 1 of the following criteria:
Quantifiable serum M-protein value (>1 g/dL of immunoglobulin (Ig)G or IgM M-protein, >0.5g/dL of IgA M-protein, >0.5 g/dL of IgD M-protein)
Urine light-chain excretion ≥200 mg/24 hours
Voluntary written informed consent must be given before performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

Exclusion Criteria:

Diagnosis of smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS). Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of lytic bone lesions. MGUS is defined by presence of serum monoclonal protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the monoclonal protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less.
Diagnosis of Waldenström's disease or other conditions in which immunoglobulin M (IgM) M-protein is present in the absence of a clonal plasma cell infiltration or lytic bone lesions.
Previously or currently treated with any systemic therapy for multiple myeloma. Prior treatment of hypercalcemia or spinal cord compression with corticosteroids or radiation therapy, respectively, does not disqualify the subject (the dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in 2-week period).
Radiation therapy within 2 weeks before randomization. Enrollment of patients who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery)
History of allergy to any of the study medications, their analogues, or excipients in the various formulations
≥Grade 2 peripheral neuropathy on clinical examination within 21 days before enrollment.
Any of the following clinical laboratory values within 21 days prior to enrollment:
Absolute neutrophil count (ANC) <1000 cells/mm^3
Platelets <100,000 × 10^{9/L, or <70 × 10}9/L if thrombocytopenia is considered by the investigator to be due to myeloma infiltration of bone marrow
Aspartate aminotransferase [serum glutamic oxaloacetic transaminase] (AST [SGOT]) or alanine aminotransferase [serum glutamic-pyruvic transaminase] (ALT [SGPT])

2× the upper limit of normal (ULN)

Serum creatinine >2 mg/dL (>176.8 µmol/L); if the rise in creatinine is related to myeloma and there has been demonstrated a response to hydration, the subject may be enrolled.
Myocardial infarction within 6 months prior to enrollment or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the investigator. Prior to study entry, any abnormality on electrocardiogram at screening must be determined and documented by the investigator as not medically relevant.
Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the patient at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical conditions or psychiatric illness likely to interfere with participation in this clinical study.
Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer, or other cancer for which the patient has been disease-free for at least 3 years.
Female who is pregnant or breastfeeding. Female participants of childbearing potential must have a negative pregnancy test with a sensitivity of at least 50 mIU/mL during Screening.
Use of any investigational drugs within 30 days before randomization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Hematology Oncology Assciates, LLC	Birmingham	Alabama	United States	35205
2	Desert Oasis Cancer Center	Casa Grande	Arizona	United States	85222
3	Northern Arizona Hematology & Oncology Associates - AOA	Sedona	Arizona	United States	86336
4	Arizona Oncology Associates	Tucson	Arizona	United States	85704
5	Heritage Physician Group Oncology	Hot Springs	Arkansas	United States	71913
6	Hematology Oncology Services of Arkansas	Little Rock	Arkansas	United States	72205
7	Pacific Cancer Medical Centre	Anaheim	California	United States	92801
8	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211-1850
9	Compassionate Cancer Care Medical Group	Corona	California	United States	92882
10	Compassionate Cancer Care Medical Group, Inc.	Fountain Valley	California	United States	92708
11	Robert A. Moss, MD, FACP, Inc.	Fountain Valley	California	United States	92708
12	Cancer Care Associates	Fresno	California	United States	93720
13	Glendale Memorial Hospital & Health Center	Glendale	California	United States	91204
14	California Cancer Care	Greenbrae	California	United States	94904
15	Beaver Medical Group	Highland	California	United States	92346
16	Edward A. Wagner, MD	Laguna Beach	California	United States	92882
17	Clinical Trials and Research Associates, Inc.	Montebello	California	United States	90640
18	Medical Oncology Care Associates	Orange	California	United States	92868
19	Ventura County Hematology Oncology Specialists	Oxnard	California	United States	93030
20	Southwest Cancer Care	Poway	California	United States	92064
21	Desert Cancer Care, Incorporated	Rancho Mirage	California	United States	92270
22	Compassionate Cancer Care Medical Group, Inc.	Riverside	California	United States	92501
23	Sutter Cancer Center	Sacramento	California	United States	95816
24	Cancer Research & Prevention Center	Soquel	California	United States	95073
25	Stockton Hematology/Oncology	Stockton	California	United States	95204
26	Trivalley Oncology Hematology	Westlake Village	California	United States	91361
27	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
28	Cancer Center of Central Connecticut	Southington	Connecticut	United States	06489
29	Christiana Care Health Services	Newark	Delaware	United States	19718
30	The Center for Hematology-Oncology	Boca Raton	Florida	United States	33486
31	Pasco Hernando Oncology	Brooksville	Florida	United States	34613
32	Northwest Oncology & Hematology Associates	Coral Springs	Florida	United States	33065
33	Florida Cancer Specialists	Fort Myers	Florida	United States	33901
34	Horizon Institute for Clinical Research	Hollywood	Florida	United States	33021
35	Baptist Cancer Institute	Jacksonville	Florida	United States	32207
36	University of Florida- Jacksonville	Jacksonville	Florida	United States	32209
37	Cancer Care of North Florida	Lake City	Florida	United States	32024
38	Lakeland Regional Cancer Center	Lakeland	Florida	United States	33805
39	Cancer & Blood Disease Center	Lecanto	Florida	United States	34461
40	Pasco Hernando Oncology	New Port Richey	Florida	United States	34652
41	Florida Cancer Institute	New Port Richey	Florida	United States	34655
42	Innovative Medical Research of South Florida Inc.	North Miami Beach	Florida	United States	33179
43	Ocala Oncology Center	Ocala	Florida	United States	34474
44	Cancer Centers of Florida, P.A.	Ocoee	Florida	United States	34761
45	MD Anderson Cancer Center Orlando	Orlando	Florida	United States	32806
46	Hematology Oncology Associates of the Treasure Coast, PA	Port St. Lucie	Florida	United States	34952
47	Gulfcoast Oncology Associates	St. Petersburg	Florida	United States	33705
48	S. Florida Oncology/ Hematology	West Palm Beach	Florida	United States	33458
49	Medical Oncology Associates of Augusta	Augusta	Georgia	United States	30901
50	Central Georgia Cancer Care	Macon	Georgia	United States	31201
51	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia	United States	30060
52	Summit Cancer Care	Savannah	Georgia	United States	31405
53	St. Lukes Mountain States Tumor Institute	Boise	Idaho	United States	83712
54	Snake River Oncology of Eastern Idaho, PLLC.	Idaho Falls	Idaho	United States	83404
55	Cancer Care & Hematology Specialists of Chicagoland	Arlington Heights	Illinois	United States	60005
56	Hematology Oncology Associates of Illinois	Chicago	Illinois	United States	60611
57	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612
58	University of Chicago	Chicago	Illinois	United States	60637
59	Hematology Oncology Associates of Illinois	Chicago	Illinois	United States	60657
60	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
61	Oncology Hematology Associates of North Illinois Ltd.	Gurnee	Illinois	United States	60031-3399
62	Midwest Center for Hematology / Oncology	Joliet	Illinois	United States	60432
63	Joliet Oncology-Hematology Associates, Ltd.	Joliet	Illinois	United States	60435
64	Hematology Oncology Consultants, Inc.	Naperville	Illinois	United States	60540
65	Cancer Care and Hematology Specialists of Chicagoland	Niles	Illinois	United States	60714
66	Mid-Illinois Hem & Onc	Normal	Illinois	United States	61761
67	Quincy Medical Group	Quincy	Illinois	United States	62301
68	Deaconess Clinic Incorporated	Evansville	Indiana	United States	47713
69	Central Indiana Cancer Centers	Indianapolis	Indiana	United States	46227
70	Investigative Clinical Research of Indiana, LLC	Indianapolis	Indiana	United States	46254
71	Clarian Arnett Cancer Center	Lafayette	Indiana	United States	47904
72	Medical Consultants, PC	Muncie	Indiana	United States	47303
73	Cancer Care Center	New Albany	Indiana	United States	47150
74	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
75	Hope Center	Terre Haute	Indiana	United States	47802
76	McFarland Clinic, P.C.	Ames	Iowa	United States	50010
77	Heartland Hematology-Oncology Associates, Inc.	Council Bluffs	Iowa	United States	51503
78	Siouxland Hematology/Oncology Assoc., LLP	Sioux City	Iowa	United States	51101
79	Kansas City Cancer Centers - Southwest	Overland Park	Kansas	United States	66210
80	Cancer Center of Kansas	Wichita	Kansas	United States	67214
81	Commonwealth Cancer Center	Danville	Kentucky	United States	40422
82	Kentucky Cancer Clinic	Hazard	Kentucky	United States	41701
83	Western Kentucky Hematology and Oncology Group	Paducah	Kentucky	United States	42003
84	Christus St. Francis Cabrini Cancer Center	Alexandria	Louisiana	United States	71301
85	Hematology-Oncology Clinic	Baton Rouge	Louisiana	United States	70809
86	Annapolis Oncology Center	Annapolis	Maryland	United States	21401
87	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
88	St. Agnes Health Care	Baltimore	Maryland	United States	21229
89	Auerbach Hematology Oncology Associates	Baltimore	Maryland	United States	21237
90	Maryland Hematology Oncology Association	Baltimore	Maryland	United States	21237
91	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
92	Oncology-Hematology Associates, P.A.	Clinton	Maryland	United States	20735
93	Maryland Oncology Hematology, PA	Columbia	Maryland	United States	21044
94	Carroll County Cancer Center	Westminster	Maryland	United States	21157
95	Boston Medical Center	Boston	Massachusetts	United States	02118
96	Fallon Clinic at Worcester Medical Center	Worcester	Massachusetts	United States	01608-1320
97	Henry Ford Health System	Detroit	Michigan	United States	48202
98	Cancer & Hematology Centers of Western Michigan	Grand Rapids	Michigan	United States	49546
99	Kalamazoo Hematology and Oncology	Kalamazoo	Michigan	United States	49048
100	Hematology Oncology Associates of Ohio & Michigan, PC	Lambertville	Michigan	United States	48144
101	Breslin Cancer Center / Great Lakes Cancer Institute	Lansing	Michigan	United States	48910
102	Providence Cancer Center	Southfield	Michigan	United States	48075
103	Oncology Care Associates, P.L.L.C.	St. Joseph	Michigan	United States	49085
104	Osteopathic Medical Hematology & Oncology	Woodhaven	Michigan	United States	48183
105	St. Luke's Hospital	Duluth	Minnesota	United States	55805
106	Metro MN CCOP	Minneapolis	Minnesota	United States	55416
107	Hubert H. Humphrey Cancer Center	Robbinsdale	Minnesota	United States	55422
108	St. Louis Cancer Center	Chesterfield	Missouri	United States	63017
109	Capital Region Medical Center/Cancer Center	Jefferson City	Missouri	United States	65109
110	Heartland Hematology-Oncology Associates, Inc.	Kansas City	Missouri	United States	64118
111	Kansas City Veterans Administration Medical Center	Kansas City	Missouri	United States	64128
112	St. Joseph Oncology	St. Joseph	Missouri	United States	64507
113	Great Falls Clinic, LLP	Great Falls	Montana	United States	59405
114	Great Plains Regional Medical Center	North Platte	Nebraska	United States	69101
115	Creighton Cancer Center	Omaha	Nebraska	United States	68131-2137
116	Las Vegas Cancer Center	Henderson	Nevada	United States	89052
117	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
118	Veterans Affairs New Jersey Healthcare System	East Orange	New Jersey	United States	07018
119	Drs. Forte, Schleider, Attas and Condemi, PA	Englewood	New Jersey	United States	07631
120	St. Barnabas Medical Center	Livingston	New Jersey	United States	07039
121	Newark Beth Israel Hospital	Newark	New Jersey	United States	07112
122	Somerset Hematology Oncology Associates	Somerville	New Jersey	United States	08876
123	Sparta Cancer Center	Sparta	New Jersey	United States	07871
124	New Mexico Cancer Care Associates	Santa Fe	New Mexico	United States	87505
125	Stratton VA Medical Center IRB	Albany	New York	United States	12208
126	Eastchester Center for Cancer Care	Bronx	New York	United States	10469
127	Buffalo Institute for Medical Research, Inc.	Buffalo	New York	United States	14215
128	Erie County Medical Center	Buffalo	New York	United States	14215
129	Goshen Medical Associates	Goshen	New York	United States	10924
130	Huntington Medical Group	Huntington Station	New York	United States	11746
131	North Shore-Long Island Jewish Health System	Lake Success	New York	United States	11042
132	Arena Oncology Associates	New Hyde Park	New York	United States	11042
133	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
134	New York Presbyterian Hospital-Cornell Campus	New York	New York	United States	10021
135	Interlakes Foundation, Inc.	Rochester	New York	United States	14623
136	Richmond University Medical Center	Staten Island	New York	United States	10301
137	SUNY Upstate Medical University	Syracuse	New York	United States	13210
138	New York Medical College	Valhalla	New York	United States	10595
139	Cancer Care of WNC	Asheville	North Carolina	United States	28801
140	Alamance Regional Medical Center	Burlington	North Carolina	United States	27215
141	Blood and Cancer Clinic	Fayetteville	North Carolina	United States	28304
142	Gaston Hematology & Oncology	Gastonia	North Carolina	United States	28054
143	Carolina Oncology Specialist, PA	Hickory	North Carolina	United States	28603
144	Emerywood Hematology/Oncology	High Point	North Carolina	United States	27262
145	Raleigh Hematology Oncology / Associates, P.C.	Raleigh	North Carolina	United States	27607
146	Hanover Medical Specialists, P.A.	Wilmington	North Carolina	United States	28401
147	St. Alexius Clinical Research Services	Bismark	North Dakota	United States	58501
148	Gabrail Cancer Center	Canton	Ohio	United States	44718
149	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45215
150	Oncology Partners Network	Cincinnati	Ohio	United States	45247
151	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
152	Hematology Oncology Consultants Inc.	Columbus	Ohio	United States	43235
153	Dayton Clinical Oncology Program	Dayton	Ohio	United States	45429
154	Dayton Oncology & Hematology	Kettering	Ohio	United States	45409
155	Toledo Community Hospital Oncology Program	Toledo	Ohio	United States	43617
156	Trilogy Cancer Center	Wooster	Ohio	United States	44691
157	Cancer Care Associates	Oklahoma City	Oklahoma	United States	73112
158	Oklahoma Oncology and Hematology	Tulsa	Oklahoma	United States	74136
159	Willamette Valley Cancer Center	Eugene	Oregon	United States	97401
160	Onc-Hem of Lehigh Valley, PC	Bethlehem	Pennsylvania	United States	18015
161	Hematology & Oncology Associates of NEPA	Dunmore	Pennsylvania	United States	18512
162	Medical Oncology Associates	Kingston	Pennsylvania	United States	18704
163	Regional Hematology Oncology Associates	Langhorne	Pennsylvania	United States	19047
164	Greater Philadelphia Cancer and Hematology Specialists, PC	Philadelphia	Pennsylvania	United States	19114
165	UPMC Cancer Pavillioin	Pittsburgh	Pennsylvania	United States	15232
166	Guthrie Research Institute	Sayre	Pennsylvania	United States	18840
167	Scranton Hematology Oncology	Scranton	Pennsylvania	United States	18510
168	Roger Williams Medical Center	Providence	Rhode Island	United States	02908
169	MUSC Hollings Cancer Center	Charleston	South Carolina	United States	29425
170	Cancer Center of the Carolinas	Greenville	South Carolina	United States	29605
171	Low Country Hematology & Oncology	Mt. Pleasant	South Carolina	United States	29464
172	Santee Hematology/Oncology	Sumter	South Carolina	United States	29150
173	Avera Research Institute	Sioux Falls	South Dakota	United States	57105
174	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee	United States	37404
175	The Family Cancer Center, PLLC	Collierville	Tennessee	United States	38017
176	The Cancer Center of Cookeville Regional Medical Center	Cookeville	Tennessee	United States	38501
177	The Jones Clinic	Germantown	Tennessee	United States	38138
178	East Tennessee Oncology/Hematology	Knoxville	Tennessee	United States	37920
179	University of Tennesee Medical Center	Knoxville	Tennessee	United States	37920
180	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
181	Texas Cancer Center	Abilene	Texas	United States	79606-5208
182	Texas Oncology, P.A.	Arlington	Texas	United States	76014
183	Southwest Regional Cancer Center	Austin	Texas	United States	78705
184	Texas Oncology, PA	Austin	Texas	United States	78731
185	Texas Oncology, PA	Beaumont	Texas	United States	77702
186	Texas Oncology, P.A.	Bedford	Texas	United States	76022
187	Coastal Bend Cancer Center	Corpus Christi	Texas	United States	73112
188	South Texas Institute of Cancer and Blood Disorders	Corpus Christi	Texas	United States	78405
189	Texas Oncology	Dallas	Texas	United States	75230-2510
190	Dallas Oncology Consultants	Dallas	Texas	United States	75237
191	Texas Oncology, PA / Methodist Charlton Cancer Center	Dallas	Texas	United States	75237
192	Texas Oncology PA	Dallas	Texas	United States	75246
193	Texas Cancer Center	Denton	Texas	United States	76210
194	El Paso Cancer Treatment Center	El Paso	Texas	United States	79902
195	Texas Cancer Center	Fort Worth	Texas	United States	76104
196	Texas Oncology, PA	Garland	Texas	United States	75042
197	Lee C. Drinkard, MD	Grapevine	Texas	United States	76051
198	Houston Cancer Institute	Houston	Texas	United States	77055
199	Medicus Alliance Clinical Research Organization, LLC	Houston	Texas	United States	77090
200	Lake Vista Cancer Center	Lewisville	Texas	United States	75067
201	Longview Cancer Center	Longview	Texas	United States	75601
202	Texas Cancer Center of Mesquite	Mesquite	Texas	United States	75150
203	Texas Oncology, P.A.	Midland	Texas	United States	79701
204	Texas Oncology - Odessa	Odessa	Texas	United States	79761
205	Paris Regional Cancer Center	Paris	Texas	United States	75460
206	Cancer Care Network of South Texas	San Antonio	Texas	United States	78217
207	Cancer Care Center of South Texas	San Antonio	Texas	United States	78229
208	CTRC Institute for Drug Development	San Antonio	Texas	United States	78245
209	Texas Cancer Center - Sherman	Sherman	Texas	United States	75090
210	Blood and Cancer Center of East Texas	Tyler	Texas	United States	75701
211	Tyler Hematology/Oncology, PA	Tyler	Texas	United States	75701
212	Texas Oncology, PA	Tyler	Texas	United States	75702
213	Texas Oncology	Waco	Texas	United States	76712
214	Northern Utah Associates	Ogden	Utah	United States	84403
215	Utah Cancer Specialists	Salt Lake City	Utah	United States	84106
216	The University of Vermont	Burlington	Vermont	United States	05401
217	White River Junction VAMC	White River Junction	Vermont	United States	05009-001
218	Cancer Specialists of Tidewater	Chesapeake	Virginia	United States	23320
219	Fairfax/Northern Virginia Hematology/Oncology	Fairfax	Virginia	United States	22031
220	Lynchburg Hematology Oncology Clinic, Inc.	Lynchburg	Virginia	United States	24501
221	Peninsula Cancer Institute Riverside Cancer Center	Newport News	Virginia	United States	23601
222	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
223	Virginia Cancer Institute	Richmond	Virginia	United States	23230
224	Oncology and Hematology Associates of Southwest Virginia, Inc.	Salem	Virginia	United States	24153
225	Masoom Kandahari, MD, PC	Woodbridge	Virginia	United States	22191
226	Puget Sound Cancer Center - Edmonds	Edmonds	Washington	United States	98026
227	Providence Everett Medical Center	Everett	Washington	United States	98201
228	Puget Sound Cancer Center, Inc	Seattle	Washington	United States	98133
229	Cancer Care Northwest, US Oncology	Spokane	Washington	United States	99202
230	Northwest Medical Specialties, PLLC	Tacoma	Washington	United States	98405
231	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801
232	Yakima Valley Memorial Hospital / North Star Lodge	Yakima	Washington	United States	98902
233	Gundersen Clinic, Ltd.	La Crosse	Wisconsin	United States	54601
234	Alyce & Elmore Kraemer Cancer Center	West Bend	Wisconsin	United States	53095
235	Hospital Auxillo Mutuo, Auxilio Mutuo Cancer Center	San Juan		Puerto Rico	00919-1227

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Millennium Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT00507416

Other Study ID Numbers:

C05009

First Posted:

Jul 26, 2007

Last Update Posted:

May 1, 2014

Last Verified:

Mar 1, 2014

Additional relevant MeSH terms:

Multiple Myeloma

Neoplasms, Plasma Cell

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 158 investigative sites in the United States from 26 June 2007 to 28 March 2013
Pre-assignment Detail	Participants with previously untreated multiple myeloma were randomized in a 1:1:1 ratio to one of three treatment groups: VD: Velcade (bortezomib) and dexamethasone; VTD: Velcade, thalidomide, and dexamethasone; VMP: Velcade, melphalan, and prednisone.

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Period Title: Overall Study
STARTED	168	167	167
Treated (Safety Population)	165	158	163
Completed 8 Treatment Cycles	82	60	69
COMPLETED	50	42	53
NOT COMPLETED	118	125	114

Baseline Characteristics

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone	Total
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Total of all reporting groups
Overall Participants	168	167	167	502
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.6 (9.35)	71.3 (8.73)	71.3 (8.67)	71.7 (8.92)
Age, Customized (participants) [Number]
≥ 65 years	140 83.3%	135 80.8%	139 83.2%	414 82.5%
≥ 75 years	84 50%	64 38.3%	62 37.1%	210 41.8%
≥ 80 years	40 23.8%	27 16.2%	23 13.8%	90 17.9%
Sex: Female, Male (Count of Participants)
Female	67 39.9%	97 58.1%	77 46.1%	241 48%
Male	101 60.1%	70 41.9%	90 53.9%	261 52%
Race/Ethnicity, Customized (participants) [Number]
White	131 78%	124 74.3%	118 70.7%	373 74.3%
Black	23 13.7%	31 18.6%	29 17.4%	83 16.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	2 1.2%	2 0.4%
Asian	2 1.2%	1 0.6%	0 0%	3 0.6%
American Indian or Alaskan Native	0 0%	1 0.6%	2 1.2%	3 0.6%
Other	10 6%	10 6%	15 9%	35 7%
Not Reported	2 1.2%	0 0%	1 0.6%	3 0.6%
Region of Enrollment (participants) [Number]
United States	168 100%	167 100%	167 100%	502 100%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as the time from randomization to disease progression or death, whichever occurs first. Participants who did not progress and were still alive at the cut-off date were censored at the date of last contact. Response was assessed by the Investigator using the International Myeloma Working Group (IMWG) uniform response criteria. Progressive disease requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl) Urine M-component (absolute increase ≥ 200 mg/24 hours) In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 100 mg/dl) Bone marrow plasma cell percentage (absolute % ≥ 10%) Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease
Time Frame	From randomization until disease progression. Median follow-up time was 43 months.

Outcome Measure Data

Analysis Population Description
Intent-to-treat (all randomized participants)

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	168	167	167
Median (95% Confidence Interval) [months]	14.7	15.4	17.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bortezomib and Dexamethasone, Bortezomib, Thalidomide, and Dexamethasone, Bortezomib, Melphalan and Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.458
	Comments	The global difference among arms was based on the Wald test.
	Method	Wald test
	Comments

2. Secondary Outcome

Title	Percentage of Participants With an Overall Response
Description	Overall response defined as a best overall response of complete response (CR), very good partial response (VGPR) or partial response (PR), assessed by the Investigator using the IMWG uniform response criteria. CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours (h). PR requires 1 of the following: ≥50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to <200 mg/24 h, or If M-protein not measurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels, or If FLC not measurable, a ≥ 50% reduction in plasma cells, provided baseline bone marrow plasma cell percentage was ≥30%. If present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.
Time Frame	Response assessed every other cycle for up to 13 cycles (49 weeks).

Outcome Measure Data

Analysis Population Description
Response-Evaluable population, defined as all participants who received at least 1 dose of any study drug, have measurable disease at baseline, and have at least one post-baseline M-protein measurement.

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	147	133	145
Number [percentage of participants]	73 43.5%	80 47.9%	70 41.9%

3. Secondary Outcome

Title	Percentage of Participants With a Complete Response
Description	Participants with a best overall response of complete response, defined as negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. Response was assessed by the Investigator using the IMWG uniform response criteria.
Time Frame	Response assessed every other cycle, for up to 13 cycles (49 weeks).

Outcome Measure Data

Analysis Population Description
Response-Evaluable population, defined as all participants who received at least 1 dose of any study drug, have measurable disease at baseline, and have at least one post-baseline M-protein measurement.

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	147	133	145
Number [percentage of participants]	3 1.8%	4 2.4%	4 2.4%

4. Secondary Outcome

Title	Percentage of Participants With a Complete Response or a Very Good Partial Response
Description	Complete response is defined by negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow. Very good partial response is defined by serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. Response was assessed by the Investigator using the IMWG uniform response criteria.
Time Frame	Response assessed every other cycle for up to 13 cycles (49 weeks).

Outcome Measure Data

Analysis Population Description
Response-Evaluable population, defined as all participants who received at least 1 dose of any study drug, have measurable disease at baseline, and have at least one post-baseline M-protein measurement.

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	147	133	145
Number [percentage of participants]	37 22%	51 30.5%	41 24.6%

5. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined in participants with an overall response as the time between first documentation of response and disease progression. Responders without disease progression were censored at the last clinical assessment of response.
Time Frame	From first documented response until disease progression. Median follow-up time was 43 months.

Outcome Measure Data

Analysis Population Description
Participants with an overall response

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	107	106	101
Median (95% Confidence Interval) [months]	18.3	22.4	19.8

6. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time between randomization and death. Participants still alive at the cutoff date or lost to follow-up were censored at the date of last contact.
Time Frame	From randomization until death. Median follow-up time was 43 months.

Outcome Measure Data

Analysis Population Description
Intent to treat

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	168	167	167
Median (95% Confidence Interval) [months]	49.8	51.5	53.1

7. Secondary Outcome

Title	Time to Alternative Therapy
Description	Time to alternative therapy is defined as the time between randomization and alternative therapy. Participants who did not receive alternative therapy were censored at the time of last contact.
Time Frame	From randomization until alternative therapy. Median follow-up time was 43 months.

Outcome Measure Data

Analysis Population Description
Intent to Treat

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	168	167	167
Median (95% Confidence Interval) [months]	19.7	24.5	19.0

8. Secondary Outcome

Title	Change From Baseline in EORTC QLQ-C30 - Global Health Status
Description	The European Organisation 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, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement.
Time Frame	Baseline and Day 1 of Cycles 3, 5, 7, 9, 11 and 13

Outcome Measure Data

Analysis Population Description
Intent-to-treat population with available data at each time point (indicated by "n").

Arm/Group Title	Bortezomib and Dexamethasone	Bortezomib, Thalidomide, and Dexamethasone	Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).	Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
Measure Participants	168	167	167
Cycle 3, Day 1 (n=129, 115, 125)	1.3 (25.40)	-4.4 (27.04)	2.0 (30.82)
Cycle 5, Day 1 (n=114, 98, 107)	-4.9 (30.36)	-6.1 (27.47)	-0.4 (29.24)
Cycle 7, Day 1 (n=89, 79, 84)	-3.3 (32.58)	-8.6 (31.86)	-4.7 (28.61)
Cycle 9, Day 1 (n=87, 66, 67)	-4.2 (33.55)	-8.1 (28.16)	-1.0 (28.55)
Cycle 11, Day 1 (n=71, 61, 65)	-11.6 (33.67)	-7.9 (29.54)	2.8 (31.72)
Cycle 13, Day 1 (n=67, 52, 61)	-10.2 (36.00)	-8.5 (32.87)	1.0 (35.16)

Adverse Events

	Bortezomib and Dexamethasone		Bortezomib, Thalidomide, and Dexamethasone		Bortezomib, Melphalan and Prednisone
Time Frame	Adverse events were collected from the first dose of study drug through 30 days after the last dose of study drug. Treatment was administered for up to 49 weeks.
Adverse Event Reporting Description	Per protocol, all grades of peripheral neuropathy and skeletal events, Grade 3/4 AEs, and all SAEs were recorded. There may be grade 1 or 2 events that were not required to be collected.

Arm/Group Title	Bortezomib and Dexamethasone		Bortezomib, Thalidomide, and Dexamethasone		Bortezomib, Melphalan and Prednisone
Arm/Group Description	Participants received bortezomib (Velcade) 1.3 mg/m^2 administered as a bolus intravenous (IV) injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).		Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 and 12, and thalidomide 100 mg orally on Days 1-21 for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).		Participants received bortezomib 1.3 mg/m^2 administered as a bolus IV injection on Days 1, 4, 8, and 11, and melphalan 9 mg/m^2 orally on Days 1-4 every other cycle and prednisone 60 mg/m^2 orally on Days 1-4 every other cycle for eight 21-day treatment cycles (Induction). Participants then received bortezomib 1.6 mg/^2 IV on Days 1, 8, 15 and 22 for five 35-day cycles (Maintenance).
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Bortezomib and Dexamethasone		Bortezomib, Thalidomide, and Dexamethasone		Bortezomib, Melphalan and Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/165 (53.3%)		92/158 (58.2%)		83/163 (50.9%)
Blood and lymphatic system disorders
Anaemia	4/165 (2.4%)		6/158 (3.8%)		2/163 (1.2%)
Haemorrhagic anaemia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Thrombocytopenia	1/165 (0.6%)		1/158 (0.6%)		3/163 (1.8%)
Pancytopenia	0/165 (0%)		0/158 (0%)		3/163 (1.8%)
Febrile neutropenia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Neutropenia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Coagulopathy	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Cardiac disorders
Atrial fibrillation	7/165 (4.2%)		7/158 (4.4%)		1/163 (0.6%)
Atrial flutter	3/165 (1.8%)		1/158 (0.6%)		1/163 (0.6%)
Supraventricular tachycardia	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Sinus tachycardia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Cardiac failure congestive	7/165 (4.2%)		8/158 (5.1%)		1/163 (0.6%)
Angina pectoris	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Acute coronary syndrome	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Acute myocardial infarction	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Bradycardia	1/165 (0.6%)		2/158 (1.3%)		0/163 (0%)
Arrhythmia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Tachycardia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Cardiac arrest	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Cardio-respiratory arrest	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Ventricular fibrillation	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Pericardial effusion	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Right ventricular failure	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Tricuspid valve incompetence	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Orthostatic hypotension	5/165 (3%)		1/158 (0.6%)		5/163 (3.1%)
Gastrointestinal disorders
Diarrhoea	12/165 (7.3%)		5/158 (3.2%)		8/163 (4.9%)
Vomiting	3/165 (1.8%)		5/158 (3.2%)		6/163 (3.7%)
Nausea	2/165 (1.2%)		4/158 (2.5%)		4/163 (2.5%)
Constipation	6/165 (3.6%)		3/158 (1.9%)		3/163 (1.8%)
Abdominal pain	4/165 (2.4%)		3/158 (1.9%)		4/163 (2.5%)
Gastrointestinal haemorrhage	2/165 (1.2%)		4/158 (2.5%)		1/163 (0.6%)
Ileus	1/165 (0.6%)		1/158 (0.6%)		3/163 (1.8%)
Intestinal obstruction	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Pancreatitis acute	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Pancreatitis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Small intestinal obstruction	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Intestinal perforation	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Large intestinal ulcer	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Large intestine perforation	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Colitis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Colitis ischaemic	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Rectal haemorrhage	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Abdominal hernia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Faecaloma	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Gastric perforation	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Gastritis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Enterocolitis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Abdominal discomfort	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Diverticular perforation	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Intestinal ischaemia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Ileus paralytic	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Stomatitis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
General disorders
Asthenia	6/165 (3.6%)		3/158 (1.9%)		3/163 (1.8%)
Fatigue	1/165 (0.6%)		4/158 (2.5%)		2/163 (1.2%)
Pyrexia	7/165 (4.2%)		2/158 (1.3%)		2/163 (1.2%)
Pain	0/165 (0%)		1/158 (0.6%)		2/163 (1.2%)
Chest pain	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Non-cardiac chest pain	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Oedema peripheral	1/165 (0.6%)		2/158 (1.3%)		1/163 (0.6%)
Generalised oedema	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Death	2/165 (1.2%)		1/158 (0.6%)		1/163 (0.6%)
Multi-organ failure	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Chills	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Nodule	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Hepatobiliary disorders
Cholecystitis	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Cholecystitis acute	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Hepatitis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hepatitis acute	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hyperbilirubinaemia	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Immune system disorders
Anaphylactic reaction	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Infections and infestations
Pneumonia	18/165 (10.9%)		12/158 (7.6%)		10/163 (6.1%)
Lobar pneumonia	1/165 (0.6%)		2/158 (1.3%)		1/163 (0.6%)
Bronchitis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Sepsis	3/165 (1.8%)		1/158 (0.6%)		2/163 (1.2%)
Bacteraemia	1/165 (0.6%)		1/158 (0.6%)		2/163 (1.2%)
Septic shock	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Bacterial sepsis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Device related sepsis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Urosepsis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Urinary tract infection	2/165 (1.2%)		2/158 (1.3%)		4/163 (2.5%)
Pyelonephritis acute	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Gastroenteritis	1/165 (0.6%)		1/158 (0.6%)		2/163 (1.2%)
Diverticulitis	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Appendicitis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Peritonitis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Cellulitis	3/165 (1.8%)		1/158 (0.6%)		0/163 (0%)
Periorbital cellulitis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Peritonitis bacterial	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Pneumonia bacterial	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Herpes zoster	1/165 (0.6%)		0/158 (0%)		2/163 (1.2%)
Herpes zoster disseminated	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Clostridium difficile colitis	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Staphylococcal abscess	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Staphylococcal bacteraemia	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Bursitis infective	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Oesophageal candidiasis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Escherichia urinary tract infection	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Fungal skin infection	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Device related infection	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Pneumonia pneumococcal	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Viral infection	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Duodenal perforation	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Injury, poisoning and procedural complications
Spinal compression fracture	3/165 (1.8%)		5/158 (3.2%)		1/163 (0.6%)
Ankle fracture	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hip fracture	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Lower limb fracture	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Brain contusion	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Extradural haematoma	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Fall	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Fractured ischium	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Pelvic fracture	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Pubis fracture	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Laceration	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Coronary artery restenosis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Drug dispensing error	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Tendon rupture	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Rib fracture	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Humerus fracture	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Investigations
International normalised ratio increased	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Prothrombin time prolonged	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Alanine aminotransferase increased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Aspartate aminotransferase increased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hepatic enzyme increased	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Blood creatinine increased	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Klebsiella test positive	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Blood culture positive	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Blood potassium decreased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Haemoglobin decreased	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Troponin I increased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
White blood cell count decreased	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Metabolism and nutrition disorders
Dehydration	8/165 (4.8%)		6/158 (3.8%)		9/163 (5.5%)
Hypovolaemia	2/165 (1.2%)		1/158 (0.6%)		0/163 (0%)
Hyponatraemia	3/165 (1.8%)		1/158 (0.6%)		4/163 (2.5%)
Hypokalaemia	2/165 (1.2%)		3/158 (1.9%)		1/163 (0.6%)
Hyperkalaemia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hyperglycaemia	2/165 (1.2%)		2/158 (1.3%)		0/163 (0%)
Hypoglycaemia	2/165 (1.2%)		1/158 (0.6%)		1/163 (0.6%)
Hypercalcaemia	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Hypocalcaemia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Decreased appetite	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Cachexia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Failure to thrive	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Diabetes mellitus inadequate control	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Electrolyte imbalance	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Lactic acidosis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Fluid overload	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Musculoskeletal and connective tissue disorders
Back pain	3/165 (1.8%)		3/158 (1.9%)		5/163 (3.1%)
Pain in extremity	2/165 (1.2%)		2/158 (1.3%)		2/163 (1.2%)
Musculoskeletal chest pain	0/165 (0%)		0/158 (0%)		2/163 (1.2%)
Musculoskeletal pain	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Neck pain	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Muscular weakness	2/165 (1.2%)		3/158 (1.9%)		3/163 (1.8%)
Arthralgia	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Cervical spinal stenosis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Lumbar spinal stenosis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Bone pain	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Costochondritis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Intervertebral disc compression	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Osteolysis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma	1/165 (0.6%)		2/158 (1.3%)		1/163 (0.6%)
Plasmacytoma	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Cancer pain	0/165 (0%)		2/158 (1.3%)		1/163 (0.6%)
Metastases to liver	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Metastases to lung	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Nervous system disorders
Neuropathy peripheral	2/165 (1.2%)		5/158 (3.2%)		4/163 (2.5%)
Peripheral sensory neuropathy	3/165 (1.8%)		3/158 (1.9%)		0/163 (0%)
Peripheral motor neuropathy	2/165 (1.2%)		1/158 (0.6%)		0/163 (0%)
Neuralgic amyotrophy	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Syncope	5/165 (3%)		5/158 (3.2%)		5/163 (3.1%)
Lethargy	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Cerebrovascular accident	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Haemorrhage intracranial	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Spinal haematoma	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Encephalopathy	1/165 (0.6%)		2/158 (1.3%)		0/163 (0%)
Dizziness	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Dizziness postural	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Dementia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Dementia with Lewy bodies	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hepatic encephalopathy	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Metabolic encephalopathy	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hypoaesthesia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Neuralgia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
VIth nerve paralysis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Sciatica	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Cognitive disorder	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Quadriplegia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Convulsion	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Spinal cord compression	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Psychiatric disorders
Confusional state	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Depression	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Mental status changes	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Panic attack	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Acute psychosis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Withdrawal syndrome	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Renal and urinary disorders
Renal failure	2/165 (1.2%)		1/158 (0.6%)		3/163 (1.8%)
Renal failure acute	1/165 (0.6%)		2/158 (1.3%)		2/163 (1.2%)
Renal impairment	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Urinary retention	2/165 (1.2%)		0/158 (0%)		1/163 (0.6%)
Nephrolithiasis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Hydronephrosis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Renal tubular necrosis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Haematuria	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	4/165 (2.4%)		4/158 (2.5%)		2/163 (1.2%)
Pulmonary embolism	5/165 (3%)		4/158 (2.5%)		1/163 (0.6%)
Chronic obstructive pulmonary disease	2/165 (1.2%)		1/158 (0.6%)		0/163 (0%)
Asthma	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Respiratory failure	1/165 (0.6%)		2/158 (1.3%)		0/163 (0%)
Acute respiratory failure	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Pneumonitis	2/165 (1.2%)		0/158 (0%)		1/163 (0.6%)
Pneumonia aspiration	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Pulmonary hypertension	0/165 (0%)		3/158 (1.9%)		0/163 (0%)
Hypoxia	2/165 (1.2%)		0/158 (0%)		0/163 (0%)
Lung infiltration	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Pleural effusion	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Pneumothorax	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Pleuritic pain	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Vascular disorders
Hypotension	3/165 (1.8%)		3/158 (1.9%)		6/163 (3.7%)
Deep vein thrombosis	7/165 (4.2%)		4/158 (2.5%)		2/163 (1.2%)
Jugular vein thrombosis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Peripheral embolism	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Shock haemorrhagic	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Phlebitis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Other (Not Including Serious) Adverse Events
	Bortezomib and Dexamethasone		Bortezomib, Thalidomide, and Dexamethasone		Bortezomib, Melphalan and Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/165 (34.5%)		68/158 (43%)		68/163 (41.7%)
Blood and lymphatic system disorders
Leukopenia	2/165 (1.2%)		1/158 (0.6%)		12/163 (7.4%)
Lymphopenia	0/165 (0%)		2/158 (1.3%)		4/163 (2.5%)
Leukocytosis	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Lymphadenopathy	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Cardiac disorders
Pericarditis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Restrictive cardiomyopathy	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Sick sinus syndrome	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Sinus bradycardia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Ventricular extrasystoles	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Ventricular tachycardia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Ear and labyrinth disorders
Hypoacusis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Endocrine disorders
Adrenal insufficiency	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Cushingoid	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Inappropriate antidiuretic hormone secretion	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Eye disorders
Vision blurred	3/165 (1.8%)		5/158 (3.2%)		1/163 (0.6%)
Conjunctivitis	1/165 (0.6%)		2/158 (1.3%)		1/163 (0.6%)
Eye swelling	2/165 (1.2%)		0/158 (0%)		0/163 (0%)
Visual impairment	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Blepharitis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Conjunctivitis allergic	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Diplopia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Eye haemorrhage	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Eye pruritus	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Lacrimation increased	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Ocular hyperaemia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Gastrointestinal disorders
Dyspepsia	3/165 (1.8%)		3/158 (1.9%)		0/163 (0%)
Abdominal pain upper	1/165 (0.6%)		2/158 (1.3%)		1/163 (0.6%)
Abdominal distension	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Dry mouth	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Gastrooesophageal reflux disease	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Ascites	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Flatulence	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Hiatus hernia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Toothache	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
General disorders
Gait disturbance	0/165 (0%)		1/158 (0.6%)		2/163 (1.2%)
Catheter site erythema	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Drug withdrawal syndrome	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Face oedema	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Feeling jittery	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Influenza like illness	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Irritability	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Malaise	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Oedema	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Soft tissue inflammation	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Hepatobiliary disorders
Cholelithiasis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Immune system disorders
Seasonal allergy	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Infections and infestations
Oral candidiasis	1/165 (0.6%)		0/158 (0%)		4/163 (2.5%)
Upper respiratory tract infection	2/165 (1.2%)		1/158 (0.6%)		2/163 (1.2%)
Conjunctivitis bacterial	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Hordeolum	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Oral fungal infection	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Sinusitis	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Bronchopulmonary aspergillosis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Cystitis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Folliculitis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Furuncle	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Gastroenteritis viral	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Herpes zoster ophthalmic	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Localised infection	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Nasopharyngitis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Pneumococcal sepsis	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Skin bacterial infection	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Subcutaneous abscess	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Injury, poisoning and procedural complications
Avulsion fracture	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Contusion	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Excoriation	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Facial bones fracture	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Foot fracture	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Jaw fracture	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Lumbar vertebral fracture	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Thoracic vertebral fracture	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Investigations
Weight decreased	4/165 (2.4%)		2/158 (1.3%)		6/163 (3.7%)
Platelet count decreased	3/165 (1.8%)		1/158 (0.6%)		7/163 (4.3%)
Blood sodium decreased	3/165 (1.8%)		3/158 (1.9%)		3/163 (1.8%)
Blood uric acid increased	2/165 (1.2%)		3/158 (1.9%)		3/163 (1.8%)
Neutrophil count decreased	0/165 (0%)		0/158 (0%)		6/163 (3.7%)
Blood alkaline phosphatase increased	0/165 (0%)		0/158 (0%)		3/163 (1.8%)
Blood urea increased	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Protein total increased	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Weight increased	0/165 (0%)		3/158 (1.9%)		0/163 (0%)
Blood bilirubin increased	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Troponin T increased	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Blood calcium increased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Blood chloride decreased	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Blood creatinine decreased	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Blood glucose increased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Blood immunoglobulin G increased	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Blood phosphorus decreased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Blood potassium increased	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Breath sounds abnormal	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Carbon monoxide diffusing capacity decreased	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Lymphocyte count decreased	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Lymphocyte count increased	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Red blood cell count decreased	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Metabolism and nutrition disorders
Hyperuricaemia	3/165 (1.8%)		8/158 (5.1%)		4/163 (2.5%)
Hypomagnesaemia	0/165 (0%)		1/158 (0.6%)		2/163 (1.2%)
Diabetes mellitus	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Hypophosphataemia	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Gout	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Hyperlipidaemia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Hypoalbuminaemia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Vitamin B12 deficiency	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/165 (0.6%)		2/158 (1.3%)		1/163 (0.6%)
Myalgia	3/165 (1.8%)		0/158 (0%)		0/163 (0%)
Groin pain	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Flank pain	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Joint swelling	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Muscle tightness	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Musculoskeletal stiffness	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Neck mass	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Osteonecrosis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Pain in jaw	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Pathological fracture	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Rotator cuff syndrome	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Nervous system disorders
Dysgeusia	2/165 (1.2%)		4/158 (2.5%)		2/163 (1.2%)
Post herpetic neuralgia	2/165 (1.2%)		2/158 (1.3%)		1/163 (0.6%)
Tremor	2/165 (1.2%)		2/158 (1.3%)		1/163 (0.6%)
Balance disorder	2/165 (1.2%)		2/158 (1.3%)		0/163 (0%)
Paraesthesia	1/165 (0.6%)		0/158 (0%)		3/163 (1.8%)
Headache	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Peripheral sensorimotor neuropathy	0/165 (0%)		1/158 (0.6%)		2/163 (1.2%)
Somnolence	1/165 (0.6%)		2/158 (1.3%)		0/163 (0%)
Ageusia	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Cranial nerve disorder	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Dysarthria	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Memory impairment	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Ataxia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Hemiparesis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Hypogeusia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Polyneuropathy	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Presyncope	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Psychiatric disorders
Insomnia	9/165 (5.5%)		6/158 (3.8%)		6/163 (3.7%)
Anxiety	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Mood altered	2/165 (1.2%)		1/158 (0.6%)		0/163 (0%)
Disorientation	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Mood swings	2/165 (1.2%)		0/158 (0%)		0/163 (0%)
Agitation	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Anhedonia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Anxiety disorder due to a general medical condition	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Delusion	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Depressed mood	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Dysphoria	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Psychotic disorder	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Restlessness	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Renal and urinary disorders
Dysuria	2/165 (1.2%)		0/158 (0%)		3/163 (1.8%)
Pollakiuria	0/165 (0%)		1/158 (0.6%)		2/163 (1.2%)
Urinary incontinence	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Azotaemia	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Nocturia	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Reproductive system and breast disorders
Pelvic pain	2/165 (1.2%)		0/158 (0%)		0/163 (0%)
Erectile dysfunction	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Vaginal haemorrhage	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/165 (1.8%)		5/158 (3.2%)		3/163 (1.8%)
Oropharyngeal pain	2/165 (1.2%)		2/158 (1.3%)		1/163 (0.6%)
Dysphonia	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Epistaxis	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Nasal congestion	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Productive cough	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Sinus congestion	1/165 (0.6%)		1/158 (0.6%)		0/163 (0%)
Atelectasis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Dyspnoea exertional	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Rales	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Respiratory tract congestion	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Sleep apnoea syndrome	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Wheezing	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Skin and subcutaneous tissue disorders
Rash pruritic	0/165 (0%)		5/158 (3.2%)		3/163 (1.8%)
Pruritus	1/165 (0.6%)		1/158 (0.6%)		4/163 (2.5%)
Decubitus ulcer	1/165 (0.6%)		1/158 (0.6%)		1/163 (0.6%)
Rash erythematous	0/165 (0%)		1/158 (0.6%)		2/163 (1.2%)
Dermatitis	0/165 (0%)		0/158 (0%)		2/163 (1.2%)
Drug eruption	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Dry skin	0/165 (0%)		2/158 (1.3%)		0/163 (0%)
Rash macular	0/165 (0%)		1/158 (0.6%)		1/163 (0.6%)
Acne	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Alopecia	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Dermatitis allergic	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Dermatitis bullous	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Dermatitis exfoliative	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Diabetic foot	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Ecchymosis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Erythema	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Exfoliative rash	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Heat rash	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Lichenoid keratosis	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Palmar-plantar erythrodysaesthesia syndrome	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Petechiae	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Rash	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Rash maculo-papular	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Rash vesicular	0/165 (0%)		0/158 (0%)		1/163 (0.6%)
Skin lesion	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Skin ulcer	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Swelling face	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Urticaria	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Vascular disorders
Hypertension	0/165 (0%)		3/158 (1.9%)		2/163 (1.2%)
Hot flush	1/165 (0.6%)		0/158 (0%)		1/163 (0.6%)
Haematoma	1/165 (0.6%)		0/158 (0%)		0/163 (0%)
Thrombophlebitis superficial	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Thrombosis	0/165 (0%)		1/158 (0.6%)		0/163 (0%)
Withdrawal hypertension	0/165 (0%)		1/158 (0.6%)		0/163 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi-site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.

Results Point of Contact

Name/Title	Medical Director
Organization	Millennium Pharmaceuticals Inc
Phone	1-800-778-2860
Email	clinicaltrialregistry@tpna.com

Responsible Party:

Millennium Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT00507416

Other Study ID Numbers:

C05009

First Posted:

Jul 26, 2007

Last Update Posted:

May 1, 2014

Last Verified:

Mar 1, 2014

UPFRONT: Velcade,Thalidomide, and Dexamethasone Versus Velcade and Dexamethasone Versus Velcade, Melphalan, and Prednisone

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact