Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT00522392
• Collaborator: (none)
• Enrollment: 48
• Locations: 276
• Arms: 2
• Duration (Months): 82
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase III trial compares bortezomib, dexamethasone, and lenalidomide with bortezomib and dexamethasone to see how well they work in treating patients with multiple myeloma previously treated with dexamethasone. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bortezomib and dexamethasone is more effective with or without lenalidomide in treating multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma	Drug: bortezomib; Drug: lenalidomide; Drug: dexamethasone	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. To compare the progression-free survival (PFS) for two consolidation regimens: bortezomib, lenalidomide, and dexamethasone (VRD) versus bortezomib and dexamethasone (VD) only.

SECONDARY OBJECTIVES:

1. To determine the incremental ability of VRD versus VD in attaining a complete response or a very good partial response (VGPR) in patients receiving induction therapy with a dexamethasone based induction regimen.

2. To compare the overall survival, measured from the time of study entry.

3. Evaluate response rate and PFS according to cytogenetic category (by gene expression and fluorescence in situ hybridization [FISH]).

4. To evaluate the toxicity of the two regimens.

5. To compare quality of life (QOL) based on the Functional Assessment of Cancer Therapy (FACT)-Neurotoxicity (Ntx) Trial Outcome Index (TOI) of patients receiving VD to those receiving VRD from registration to 6 months post consolidation treatment.

6. To examine the impact of differential treatment response (PFS), if observed, on QOL based on the FACT-Ntx TOI up to 12 months post consolidation treatment.

7. To obtain prospective data on multiple myeloma specific QOL attributes.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive bortezomib at 1.3 mg/m2 intravenously (IV) on days 1, 4, 8, and 11, lenalidomide orally (PO) once daily (QD) at 15 mg on days 1-14, and dexamethasone at 40 mg total dose per day PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive bortezomib at 1.3 mg/m2 IV on days 1, 4, 8, and 11 and dexamethasone at 40 mg total dose per day PO QD on days 1, 8, and 15. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then every 12 months for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase III Trial of Consolidation Therapy With Bortezomib (Velcade®)-Lenalidomide (Revlimid®) -Dexamethasone (VRD) Versus Bortezomib (Velcade®)-Dexamethasone (VD) for Patients With Multiple Myeloma Who Have Completed a Dexamethasone Based Induction Regimen
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (VRD) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin.	Drug: bortezomib; Given IV; Other Names: PS-341 LDP-341 MLN-341 VELCADE ; Drug: lenalidomide; Given PO; Other Names: CC-5013 CDC-501 Revlimid® (formerly Revimid®) ; Drug: dexamethasone; Given PO; Other Names: Decadron Hexadrol Dexameth Dexone DXM
Active Comparator: Arm B (VD) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15.	Drug: bortezomib; Given IV; Other Names: PS-341 LDP-341 MLN-341 VELCADE ; Drug: dexamethasone; Given PO; Other Names: Decadron Hexadrol Dexameth Dexone DXM

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years]

   Progression-free survival was defined as the time from randomization to the earliest documentation of disease progression (PD) or death. If a patient died without evidence of PD, the patient was considered an event if death occurred within 3 months of the last disease assessment. Patients who died outside of the specified interval or patients who were alive without evidence of PD were censored at the date of last disease assessment. The PFS results are based on data as of August 2012, while overall survival (OS) was updated in April 2014. Given the early termination and limited sample size, data management efforts to update PFS were not pursued.

Secondary Outcome Measures

1. Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR]) [Assessed at the end of each cycle, every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years]

   CR: Patients with complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. To be considered CR, patients must meet all of the following criteria: Negative immunofixation on the serum and urine at two consecutive times Disappearance of any soft tissue plasmacytomas ≤5% plasma cells in bone marrow If serum and urine M protein are unmeasurable and the immunoglobulin free light chain (FLC) parameter is being used, patients must have a normal ratio of 0.26-1.65 at two consecutive times VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis OR >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP) If the serum and urine M protein are unmeasurable and the immunoglobulin FLC parameter is being used, a >90% decrease in the difference between involved and uninvolved FLC levels is required in place of the M protein criteria

2. Overall Survival (OS) [Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years]

   Overall survival is defined as the time from randomization to death or date of last known alive. The OS results are based on data as of April 2014.

3. Change in Quality of Life (QOL) From Baseline to 6 Months Post Consolidation as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI) [Baseline and 6 months post consolidation treatment]

   The combined score on the FACT-Ntx TOI is of interest. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible quality of life) -100 (best possible quality of life). The primary QOL endpoint is defined as the change in the FACT-Ntx TOI score from registration to 6 months post consolidation treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Symptomatic multiple myeloma, that was symptomatic at time of initial diagnosis, but may be asymptomatic at the time of registration based on induction therapy

• For the original diagnosis of myeloma, patients must have met the following criteria at one point in their disease course: bone marrow plasmacytosis (>10% plasma cells or sheets of plasma cells) or a biopsy proven plasmacytoma, and evidence of end-organ damage due to multiple myeloma including anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fractures) or renal dysfunction.

• Patients may have prior exposure to bortezomib

• Patients must have received a minimum of 1 cycle, maximum of 6 cycles, of a dexamethasone-based regimen; patient must not have experienced progressive disease on such therapy

• The following induction regimens were considered adequate for enrollment: dexamethasone alone; vincristine, doxorubicin and dexamethasone; thalidomide and dexamethasone; lenalidomide and dexamethasone; liposomal doxorubicin and dexamethasone; the combination of any of the above agents and dexamethasone; or cyclophosphamide, lenalidomide and dexamethasone

• Patients must have received the minimum cumulative dose of dexamethasone of 160 mg (sum of induction treatment) with no maximum dose specified

• Patients must have been offered and refused front-line stem cell transplant OR not have been eligible for front-line stem cell transplant.

• Bone marrow aspiration and/or biopsy must be obtained =< 28 days prior to randomization

• All tests below must be performed =< 28 days prior to randomization:

• Kappa free light chain mg/dL

• Lambda free light chain mg/dL

• Serum M-protein by serum protein electrophoresis (SPEP)

• Urine M-protein light chain excretion by urine protein electrophoresis (UPEP)

• Adequate laboratory levels within 7 days prior to randomization: hemoglobin > 7 g/dL, platelet count > 75,000 cells/mm^{3, absolute neutrophil count > 1000 cells/mm}3, creatinine < 2.5 mg/dL, creatinine clearance (measured or calculated) >= 60 mL/min, direct bilirubin =< 1.5 mg/dL, serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 times the upper limit of normal

• Patients may be receiving bisphosphonates or erythropoietin growth factors (erythropoietic agents) for multiple myeloma

• Prior palliative and/or localized radiation therapy is permitted, provided at least 14 days have passed from date of last radiation therapy to date of randomization

• Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or coumadin (patients with prior deep vein thrombosis [DVT] are eligible provided they remain on the anticoagulation regimen that was prescribed for treatment of the DVT throughout the protocol therapy)

• Patients must be competent to understand the study as explained in the consent form

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

• Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking lenalidomide, and for 4 weeks after stopping treatment

• Patients with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months

• Age >=18 years

Exclusion Criteria:

• More than 8 weeks from the last day of last cycle of induction treatment

• Active, uncontrolled seizure disorder; seizures in the last 6 months

• Uncontrolled inter-current illness that would limit compliance with the study including uncontrolled hypertension, symptomatic congestive heart failure, unstable angina, uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation, prior history of Stevens Johnson syndrome

• Grade 2 or higher peripheral neuropathy by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

• Active, uncontrolled infection

• Smoldering myeloma or monoclonal gammopathy of undetermined significance

• Pregnant or nursing women were not eligible. Women of child-bearing potential unwilling to use a dual method of contraception and men who were unwilling to use a condom were not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Northbay Cancer Center	Fairfield	California	United States	94533
3	Kaiser Permanente	San Diego	California	United States	92120
4	Stanford University Hospitals and Clinics	Stanford	California	United States	94305
5	The Medical Center of Aurora	Aurora	Colorado	United States	80012
6	Boulder Community Hospital	Boulder	Colorado	United States	80301
7	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
8	Porter Adventist Hospital	Denver	Colorado	United States	80210
9	Exempla Saint Joseph Hospital	Denver	Colorado	United States	80218
10	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
11	Rose Medical Center	Denver	Colorado	United States	80220
12	Colorado Cancer Research Program CCOP	Denver	Colorado	United States	80224-2522
13	Swedish Medical Center	Englewood	Colorado	United States	80113
14	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81502
15	North Colorado Medical Center	Greeley	Colorado	United States	80631
16	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
17	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
18	Longmont United Hospital	Longmont	Colorado	United States	80501
19	McKee Medical Center	Loveland	Colorado	United States	80539
20	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
21	North Suburban Medical Center	Thornton	Colorado	United States	80229
22	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
23	Beebe Medical Center	Lewes	Delaware	United States	19958
24	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
25	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
26	John B Amos Cancer Center	Columbus	Georgia	United States	31904
27	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia	United States	30165
28	Saint Anthony's Health	Alton	Illinois	United States	62002
29	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
30	Graham Hospital Association	Canton	Illinois	United States	61520
31	Memorial Hospital	Carthage	Illinois	United States	62321
32	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
33	Alexian Brothers Medical and Cancer Center	Elk Grove Village	Illinois	United States	60007
34	Eureka Hospital	Eureka	Illinois	United States	61530
35	Saint Francis Hospital	Evanston	Illinois	United States	60202
36	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
37	Illinois CancerCare Galesburg	Galesburg	Illinois	United States	61401
38	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
39	Mason District Hospital	Havana	Illinois	United States	62644
40	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
41	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
42	Mcdonough District Hospital	Macomb	Illinois	United States	61455
43	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois	United States	61265
44	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois	United States	61265
45	Sharis, Christine M MD (UIA Investigator)	Moline	Illinois	United States	61265
46	Stoffel, Thomas J MD (UIA Investigator)	Moline	Illinois	United States	61265
47	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
48	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
49	Community Cancer Center Foundation	Normal	Illinois	United States	61761
50	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
51	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
52	Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
53	Pekin Hospital	Pekin	Illinois	United States	61554
54	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
55	Proctor Hospital	Peoria	Illinois	United States	61614
56	Illinois Oncology Research Association CCOP	Peoria	Illinois	United States	61615
57	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
58	Illinois Valley Hospital	Peru	Illinois	United States	61354
59	Valley Radiation Oncology	Peru	Illinois	United States	61354
60	Perry Memorial Hospital	Princeton	Illinois	United States	61356
61	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
62	Memorial Medical Center	Springfield	Illinois	United States	62781-0001
63	Carle Clinic-Urbana Main	Urbana	Illinois	United States	61801
64	Saint Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
65	Reid Hospital and Health Care Services	Richmond	Indiana	United States	47374
66	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
67	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa	United States	52722
68	Mercy Capitol	Des Moines	Iowa	United States	50307
69	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
70	Iowa Oncology Research Association CCOP	Des Moines	Iowa	United States	50309
71	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
72	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
73	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
74	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
75	Siouxland Hematology Oncology Associates	Sioux City	Iowa	United States	51101
76	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
77	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
78	Covenant Medical Center	Waterloo	Iowa	United States	50702
79	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
80	Wesley Medical Center	Wichita	Kansas	United States	67214
81	Doctors Carrol, Sheth, Raghavan	Louisville	Kentucky	United States	40215
82	Union Hospital of Cecil County	Elkton MD	Maryland	United States	21921
83	Bixby Medical Center	Adrian	Michigan	United States	49221
84	Hickman Cancer Center	Adrian	Michigan	United States	49221
85	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
86	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan	United States	48106
87	Oakwood Hospital	Dearborn	Michigan	United States	48124
88	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
89	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49431
90	Hurley Medical Center	Flint	Michigan	United States	48502
91	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
92	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
93	Allegiance Health	Jackson	Michigan	United States	49201
94	Sparrow Hospital	Lansing	Michigan	United States	48912
95	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
96	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
97	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
98	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
99	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
100	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
101	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
102	Sanford Clinic North-Bemidgi	Bemidji	Minnesota	United States	56601
103	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
104	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
105	Essentia Health Duluth Clinic CCOP	Duluth	Minnesota	United States	55805
106	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
107	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
108	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
109	Unity Hospital	Fridley	Minnesota	United States	55432
110	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
111	Meeker County Memorial Hospital	Litchfield	Minnesota	United States	55355
112	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
113	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
114	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
115	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
116	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
117	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
118	Mayo Clinic	Rochester	Minnesota	United States	55905
119	Metro-Minnesota CCOP	Saint Louis Park	Minnesota	United States	55416
120	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
121	Regions Hospital	Saint Paul	Minnesota	United States	55101
122	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota	United States	55102
123	United Hospital	Saint Paul	Minnesota	United States	55102
124	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
125	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
126	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
127	Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
128	Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
129	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
130	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
131	Capital Regional Medical Center	Jefferson City	Missouri	United States	65101
132	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
133	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
134	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
135	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
136	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
137	Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield	Springfield	Missouri	United States	65802
138	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
139	Montana Cancer Consortium CCOP	Billings	Montana	United States	59101
140	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
141	Saint Vincent Healthcare	Billings	Montana	United States	59101
142	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana	United States	59102
143	Billings Clinic	Billings	Montana	United States	59107-7000
144	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
145	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
146	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
147	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
148	Great Falls Clinic	Great Falls	Montana	United States	59405
149	Northern Montana Hospital	Havre	Montana	United States	59501
150	Saint Peter's Community Hospital	Helena	Montana	United States	59601
151	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
152	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
153	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
154	Community Medical Hospital	Missoula	Montana	United States	59801
155	Montana Cancer Specialists	Missoula	Montana	United States	59802
156	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
157	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
158	Good Samaritan Hospital	Kearney	Nebraska	United States	68847
159	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
160	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
161	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
162	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey	United States	07018-1095
163	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey	United States	08060
164	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey	United States	08043
165	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
166	Montefiore Medical Center	Bronx	New York	United States	10467-2490
167	Kings County Hospital	Brooklyn	New York	United States	11203
168	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
169	University Hospital of Brooklyn	Brooklyn	New York	United States	11203
170	Mary Imogene Bassett Hospital	Cooperstown	New York	United States	13326
171	Adirondack Cancer Center	Glens Falls	New York	United States	12801
172	Orange Regional Medical Center	Middletown	New York	United States	10940
173	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
174	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
175	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
176	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
177	Mercy Medical Center	Canton	Ohio	United States	44708
178	Case Western Reserve University	Cleveland	Ohio	United States	44106
179	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
180	Grant Medical Center	Columbus	Ohio	United States	43215
181	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
182	Doctors Hospital	Columbus	Ohio	United States	43228
183	Grandview Hospital	Dayton	Ohio	United States	45405
184	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
185	Miami Valley Hospital	Dayton	Ohio	United States	45409
186	Samaritan North Health Center	Dayton	Ohio	United States	45415
187	Dayton CCOP	Dayton	Ohio	United States	45420
188	Veteran Affairs Medical Center	Dayton	Ohio	United States	45428
189	Grady Memorial Hospital	Delaware	Ohio	United States	43015
190	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
191	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
192	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
193	Fremont Memorial Hospital	Fremont	Ohio	United States	43420
194	Wayne Hospital	Greenville	Ohio	United States	45331
195	Kettering Medical Center	Kettering	Ohio	United States	45429
196	Fairfield Medical Center	Lancaster	Ohio	United States	43130
197	Lima Memorial Hospital	Lima	Ohio	United States	45804
198	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
199	Saint Luke's Hospital	Maumee	Ohio	United States	43537
200	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
201	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
202	Licking Memorial Hospital	Newark	Ohio	United States	43055
203	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
204	Saint Charles Hospital	Oregon	Ohio	United States	43616
205	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
206	Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
207	North Coast Cancer Care	Sandusky	Ohio	United States	44870
208	Flower Hospital	Sylvania	Ohio	United States	43560
209	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
210	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
211	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
212	University of Toledo	Toledo	Ohio	United States	43614
213	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
214	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
215	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
216	Upper Valley Medical Center	Troy	Ohio	United States	45373
217	Fulton County Health Center	Wauseon	Ohio	United States	43567
218	Saint Ann's Hospital	Westerville	Ohio	United States	43081
219	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
220	Greene Memorial Hospital	Xenia	Ohio	United States	45385
221	Genesis HealthCare System	Zanesville	Ohio	United States	43701
222	Adventist Medical Center	Portland	Oregon	United States	97216
223	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
224	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
225	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
226	Doylestown Hospital	Doylestown	Pennsylvania	United States	18901
227	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
228	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
229	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
230	Pottstown Memorial Medical Center	Pottstown	Pennsylvania	United States	19464
231	Geisinger Medical Group	State College	Pennsylvania	United States	16801
232	Reading Hospital	West Reading	Pennsylvania	United States	19611
233	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania	United States	18711
234	Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
235	Mainline Health CCOP	Wynnewood	Pennsylvania	United States	19096
236	McLeod Regional Medical Center	Florence	South Carolina	United States	29506
237	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
238	University of Tennessee - Knoxville	Knoxville	Tennessee	United States	37920
239	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
240	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
241	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
242	Columbia Basin Hematology and Oncology PLLC	Kennewick	Washington	United States	99336
243	Harborview Medical Center	Seattle	Washington	United States	98104
244	Minor and James Medical PLLC	Seattle	Washington	United States	98104
245	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
246	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
247	The Polyclinic	Seattle	Washington	United States	98122
248	University of Washington Medical Center	Seattle	Washington	United States	98195
249	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801
250	The Schiffler Cancer Center of Wheeling Hospital	Wheeling	West Virginia	United States	26003
251	Wheeling Hospital	Wheeling	West Virginia	United States	26003
252	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
253	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
254	Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
255	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
256	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
257	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
258	Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
259	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
260	Gundersen Lutheran	La Crosse	Wisconsin	United States	54601
261	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin	United States	54601
262	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
263	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
264	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
265	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
266	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
267	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
268	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin	United States	54501
269	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin	United States	54868
270	Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
271	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
272	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
273	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
274	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
275	Welch Cancer Center	Sheridan	Wyoming	United States	82801
276	University Of Pretoria	Pretoria		South Africa	0002

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Study Chair: Rafael Fonseca, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

• Fonseca R, Rajkumar SV. Consolidation therapy with bortezomib/lenalidomide/ dexamethasone versus bortezomib/dexamethasone after a dexamethasone-based induction regimen in patients with multiple myeloma: a randomized phase III trial. Clin Lymphoma Myeloma. 2008 Oct;8(5):315-7. doi: 10.3816/CLM.2008.n.046.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00522392
• Other Study ID Numbers: NCI-2009-00521; NCI-2009-00521; E1A05; U10CA021115; U10CA180820
• First Posted: Aug 29, 2007
• Last Update Posted: Jun 26, 2015
• Last Verified: May 1, 2015

• Keywords provided by National Cancer Institute (NCI): Consolidation therapy; First-line therapy; Proteasome inhibitor; Thalidomide analogue; Quality of life
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Lenalidomide; Bortezomib

Study Results

Participant Flow

Recruitment Details	Participants were recruited from ECOG member institutions between September 6, 2007 and May 7, 2010.

Arm/Group Title	Arm A (VRD)	Arm B (VD)
Arm/Group Description	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Period Title: Overall Study
STARTED	23	25
Pts w/ Measurable Disease at Baseline	16	16
Pts w/ QOL Assessments Complete	12	8
COMPLETED	15	12
NOT COMPLETED	8	13

Baseline Characteristics

Arm/Group Title	Arm A (VRD)	Arm B (VD)	Total
Arm/Group Description	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO	Total of all reporting groups
Overall Participants	23	25	48
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	65	65
Sex: Female, Male (Count of Participants)
Female	8 34.8%	13 52%	21 43.8%
Male	15 65.2%	12 48%	27 56.3%
Region of Enrollment (participants) [Number]
United States	23 100%	25 100%	48 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	Progression-free survival was defined as the time from randomization to the earliest documentation of disease progression (PD) or death. If a patient died without evidence of PD, the patient was considered an event if death occurred within 3 months of the last disease assessment. Patients who died outside of the specified interval or patients who were alive without evidence of PD were censored at the date of last disease assessment. The PFS results are based on data as of August 2012, while overall survival (OS) was updated in April 2014. Given the early termination and limited sample size, data management efforts to update PFS were not pursued.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Arm A (VRD)	Arm B (VD)
Arm/Group Description	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Measure Participants	23	25
Median (95% Confidence Interval) [Months]	NA	17.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (VRD), Arm B (VD)
	Comments	Stratified log rank test was used to compare progression-free survival between the two arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.092
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Response Rates (Complete Response [CR] or Very Good Partial Response [VGPR])
Description	CR: Patients with complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. To be considered CR, patients must meet all of the following criteria: Negative immunofixation on the serum and urine at two consecutive times Disappearance of any soft tissue plasmacytomas ≤5% plasma cells in bone marrow If serum and urine M protein are unmeasurable and the immunoglobulin free light chain (FLC) parameter is being used, patients must have a normal ratio of 0.26-1.65 at two consecutive times VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis OR >=90% reduction in serum M-component plus urine M-component <100 mg per 24 hours (by SPEP and UPEP) If the serum and urine M protein are unmeasurable and the immunoglobulin FLC parameter is being used, a >90% decrease in the difference between involved and uninvolved FLC levels is required in place of the M protein criteria
Time Frame	Assessed at the end of each cycle, every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years

Outcome Measure Data

Analysis Population Description

Patients with measurable disease at randomization were included in this analysis.

Arm/Group Title	Arm A (VRD)	Arm B (VD)
Arm/Group Description	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Measure Participants	16	16
Number (95% Confidence Interval) [Proportion of patients]	0.625	0.188

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (VRD), Arm B (VD)
	Comments	Fisher's exact test was used to compare the response rates between the two arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the time from randomization to death or date of last known alive. The OS results are based on data as of April 2014.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, every 12 months if patient is 6-10 years from study entry, up to 10 years

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Arm A (VRD)	Arm B (VD)
Arm/Group Description	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Measure Participants	23	25
Median (95% Confidence Interval) [Months]	64.0	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (VRD), Arm B (VD)
	Comments	Stratified log-rank test was used to compare overall survival between the two arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Change in Quality of Life (QOL) From Baseline to 6 Months Post Consolidation as Assessed by the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI)
Description	The combined score on the FACT-Ntx TOI is of interest. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible quality of life) -100 (best possible quality of life). The primary QOL endpoint is defined as the change in the FACT-Ntx TOI score from registration to 6 months post consolidation treatment.
Time Frame	Baseline and 6 months post consolidation treatment

Outcome Measure Data

Analysis Population Description

Patients with both assessments complete at baseline and 6 months post consolidation treatment were included in this analysis.

Arm/Group Title	Arm A (VRD)	Arm B (VD)
Arm/Group Description	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin. bortezomib: Given IV lenalidomide: Given PO dexamethasone: Given PO	Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. bortezomib: Given IV dexamethasone: Given PO
Measure Participants	12	8
Mean (Full Range) [units on a scale]	-7.9	-2.6

Adverse Events

Time Frame	Assessed every 21 days while on treatment and for 30 days after the end of treatment
Arm/Group Title	Arm A (VRd Regimen)		Arm B (Vd Regimen)
Arm/Group Description	Arm A (VRd Regimen) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib, dexamethasone and lenalidomide. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11; fixed dose of lenalidomide at 15 mg orally on days 1-14; and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15. Aspirin 325 mg/day orally on days 1-21 of each cycle was required unless the patient was treated with alternate prophylaxis of either low molecular weight heparin or coumadin.		Arm B (Vd Regimen) Patients were given consolidation therapy for 8 cycles (1 cycle = 21 days) with the combination bortezomib plus dexamethasone. Patients received each cycle: the standard dose of bortezomib (1.3 mg/m2) on days 1, 4, 8 and 11 and 3 days of dexamethasone at 40 mg total dose per day given on days 1, 8 and 15.
All Cause Mortality
	Arm A (VRd Regimen)		Arm B (Vd Regimen)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A (VRd Regimen)		Arm B (Vd Regimen)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/23 (65.2%)		16/25 (64%)
Blood and lymphatic system disorders
Hemoglobin	0/23 (0%)		1/25 (4%)
Cardiac disorders
Sinus bradycardia	1/23 (4.3%)		0/25 (0%)
Eye disorders
Cataract	1/23 (4.3%)		0/25 (0%)
Gastrointestinal disorders
Constipation	1/23 (4.3%)		0/25 (0%)
Diarrhea w/o prior colostomy	1/23 (4.3%)		4/25 (16%)
Nausea	1/23 (4.3%)		1/25 (4%)
Vomiting	0/23 (0%)		1/25 (4%)
Abdomen, pain	1/23 (4.3%)		2/25 (8%)
General disorders
Fatigue	3/23 (13%)		4/25 (16%)
Fever w/o neutropenia	0/23 (0%)		1/25 (4%)
Infections and infestations
Infection w/ gr3-4 neut, lung	0/23 (0%)		1/25 (4%)
Infection Gr0-2 neut, colon	0/23 (0%)		2/25 (8%)
Infection Gr0-2 neut, lung	1/23 (4.3%)		1/25 (4%)
Investigations
Leukocytes	1/23 (4.3%)		0/25 (0%)
Lymphopenia	3/23 (13%)		1/25 (4%)
Neutrophils	0/23 (0%)		2/25 (8%)
Platelets	2/23 (8.7%)		0/25 (0%)
ALT, SGPT	1/23 (4.3%)		0/25 (0%)
Metabolism and nutrition disorders
Hypokalemia	1/23 (4.3%)		0/25 (0%)
Musculoskeletal and connective tissue disorders
Nonneuropathic lower extr muscle weak	1/23 (4.3%)		0/25 (0%)
Extremity-limb, pain	2/23 (8.7%)		2/25 (8%)
Joint, pain	0/23 (0%)		1/25 (4%)
Nervous system disorders
Neuropathy-motor	2/23 (8.7%)		0/25 (0%)
Neuropathy-sensory	6/23 (26.1%)		6/25 (24%)
Syncope	1/23 (4.3%)		0/25 (0%)
Psychiatric disorders
Insomnia	1/23 (4.3%)		0/25 (0%)
Psychosis	0/23 (0%)		1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/23 (4.3%)		0/25 (0%)
Skin and subcutaneous tissue disorders
Pruritus/itching	1/23 (4.3%)		0/25 (0%)
Rash/desquamation	1/23 (4.3%)		0/25 (0%)
Vascular disorders
Hypotension	0/23 (0%)		1/25 (4%)
Other (Not Including Serious) Adverse Events
	Arm A (VRd Regimen)		Arm B (Vd Regimen)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/23 (34.8%)		11/25 (44%)
Blood and lymphatic system disorders
Hemoglobin	2/23 (8.7%)		4/25 (16%)
Gastrointestinal disorders
Constipation	1/23 (4.3%)		2/25 (8%)
General disorders
Fatigue	3/23 (13%)		4/25 (16%)
Investigations
Leukocytes	1/23 (4.3%)		2/25 (8%)
Lymphopenia	1/23 (4.3%)		3/25 (12%)
Neutrophils	0/23 (0%)		2/25 (8%)
Platelets	1/23 (4.3%)		4/25 (16%)
Metabolism and nutrition disorders
Hyperglycemia	2/23 (8.7%)		1/25 (4%)
Nervous system disorders
Neuropathy-sensory	4/23 (17.4%)		4/25 (16%)
Psychiatric disorders
Insomnia	3/23 (13%)		2/25 (8%)
Skin and subcutaneous tissue disorders
Rash/desquamation	2/23 (8.7%)		1/25 (4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.