EVOLUTION: Phase 1/2 Study of VELCADE® in Combination With Other Drugs to Treat Previously Untreated Multiple Myeloma Patients

• Sponsor: Millennium Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00507442
• Collaborator: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (Industry)
• Enrollment: 158
• Locations: 2
• Arms: 4
• Duration (Months): 39
• Patients Per Site: 79
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of this Phase 1/2 study is to evaluate the efficacy and safety of treatment with VELCADE, dexamethasone, and Revlimid® (VDR) as well as VELCADE, dexamethasone, cyclophosphamide, and Revlimid (VDCR) in patients with multiple myeloma who have received no prior treatment. This study will evaluate whether the addition of Revlimid to VELCADE and Dexamethasone will increase the complete response (CR)/ very good partial response (VGPR) rate.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: cyclophosphamide; Drug: Revlimid (lenalidomide)	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 158 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of VELCADE® (Bortezomib), Dexamethasone, and Revlimid® (Lenalidomide) Versus VELCADE, Dexamethasone, Cyclophosphamide, and Revlimid Versus VELCADE, Dexamethasone and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VDR VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide)	Drug: VELCADE (bortezomib); bortezomib 1.3 mg/m^2 given via IV on days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on days 1, 8, 15 and 22 of a 6-week cycle for 4 cycles (maintenance).; Drug: dexamethasone; dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop; Drug: Revlimid (lenalidomide); lenalidomide 25 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDR arm) lenalidomide 15 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDCR arm)
Experimental: VDCR VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide)	Drug: VELCADE (bortezomib); bortezomib 1.3 mg/m^2 given via IV on days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on days 1, 8, 15 and 22 of a 6-week cycle for 4 cycles (maintenance).; Drug: dexamethasone; dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop; Drug: cyclophosphamide; cyclophosphamide 500 mg/m^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop; Drug: Revlimid (lenalidomide); lenalidomide 25 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDR arm) lenalidomide 15 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDCR arm)
Experimental: VDC VELCADE (bortezomib), dexamethasone, cyclophosphamide	Drug: VELCADE (bortezomib); bortezomib 1.3 mg/m^2 given via IV on days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on days 1, 8, 15 and 22 of a 6-week cycle for 4 cycles (maintenance).; Drug: dexamethasone; dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop; Drug: cyclophosphamide; cyclophosphamide 500 mg/m^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop
Experimental: VDC-mod Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide	Drug: VELCADE (bortezomib); bortezomib 1.3 mg/m^2 given via IV on days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on days 1, 8, 15 and 22 of a 6-week cycle for 4 cycles (maintenance).; Drug: dexamethasone; dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop; Drug: cyclophosphamide; cyclophosphamide 500 mg/m^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Combined Complete Response and Very Good Partial Response [Up to 48 weeks or until disease progression]

   Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. Very good partial response requires 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 h

Secondary Outcome Measures

1. Number of Patients With Adverse Events (AEs) [From first dose of study drug through the 30 day post-treatment AE assessment visit]

   Evaluate the safety and tolerability of the combination therapy

2. Number of Patients With Overall Response [Up to 48 weeks or until disease progression]

   Overall Response includes complete response and partial response. Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. Partial response requires at least 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by at least 90% or to < 200 mg per 24 hour.

3. Number of Patients With Stringent Complete Response Rate [Up to 48 weeks or until disease progression]

   Stringent Complete Response is defined as complete response plus normal free light chain (kappa/lambda) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

4. Number of Patients With Complete Response Rate + Near Complete Response Rate [Up to 48 weeks or until disease progression]

   Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. Near Complete response requires positive immunofixation on the serum and/or urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.

5. Duration of Response [Up to 48 weeks or until disease progression]

   Duration of response is the time from date of first documented confirmed response to date of first documented progressive disease. A confirmed response is a response that has been observed on at least two consecutive assessments. Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.

6. Time to Disease Progression [Up to 48 weeks or until disease progression]

   Time to disease progression is defined as time from the date of randomization to the date of first documented progressive disease. Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.

7. Time to Response [Up to 48 weeks or until disease response]

   Time to response is defined as time from date of randomization to the date of the first documentation of a confirmed response. confirmed response is a response that has been observed on at least two consecutive assessments.

8. Progression-free Survival [Up to 48 weeks or until disease progression/death]

   Progression-free survival is defined as time from the date of randomization to the date of the first documented progressive disease or death. Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.

9. Probability of 1-year Survival [survival probability at 1 year after randomization]

10. Overall Survival [Up to 48 weeks or until death]

    Overall survival is defined as time from the date of randomization to the date of death

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Voluntary written informed consent

• Male or female subject 18 years of age or older

• A Karnofsky Performance Status score of ≥50% (Eastern Cooperative Oncology Group Performance Status score ≤2)

• Subjects must have symptomatic myeloma or asymptomatic myeloma with myeloma-related organ damage

• Diagnosed Multiple myeloma

• Subjects must have measurable disease requiring systemic therapy

• Subjects must not have been treated previously with any systemic therapy for multiple myeloma

• Two weeks must have elapsed since the date of the last radiotherapy treatment

• Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (1 highly effective method and 1 additional effective method) used at the same time, beginning at least 4 weeks before initiation of Revlimid treatment. Women must also agree to ongoing pregnancy testing

• Men must agree to not father a child and agree to use a latex condom during therapy and for 4 weeks after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential

• All subjects must agree to comply with the requirements of the RevAssistSM program

Exclusion Criteria:

• History of allergy to any of the study medications, their analogues, or excipients in the various formulations

• ≥Grade 2 peripheral neuropathy on clinical examination

• Myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities.

• Female subject who is pregnant or breast-feeding

• Clinically relevant active infection or serious comorbid medical conditions

• Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical or psychiatric illness likely to interfere with participation in this clinical study

• Active prior malignancy diagnosed or treated within the last 3 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
2	Mayo Clinic	Rochester	Minnesota	United States	55904-0001

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

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: NCT00507442
• Other Study ID Numbers: C05008
• First Posted: Jul 26, 2007
• Last Update Posted: Jul 26, 2013
• Last Verified: Apr 1, 2012

• Keywords provided by Millennium Pharmaceuticals, Inc.: Treatment for patients with multiple myeloma; who have received no prior treatment
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Cyclophosphamide; Lenalidomide; Bortezomib

Study Results

Participant Flow

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 100 - 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Period Title: Overall Study
STARTED	42	66	33	17
COMPLETED	26	39	18	12
NOT COMPLETED	16	27	15	5

Baseline Characteristics

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod	Total
Arm/Group Description	VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 100 - 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.	Total of all reporting groups
Overall Participants	42	66	33	17	158
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	27 64.3%	42 63.6%	21 63.6%	11 64.7%	101 63.9%
>=65 years	15 35.7%	24 36.4%	12 36.4%	6 35.3%	57 36.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.5 (8.76)	60.9 (8.97)	61.4 (8.32)	59.6 (9.16)	60.5 (8.75)
Sex: Female, Male (Count of Participants)
Female	18 42.9%	28 42.4%	14 42.4%	10 58.8%	70 44.3%
Male	24 57.1%	38 57.6%	19 57.6%	7 41.2%	88 55.7%
Region of Enrollment (participants) [Number]
United States	42 100%	66 100%	33 100%	17 100%	158 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Combined Complete Response and Very Good Partial Response
Description	Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. Very good partial response requires 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 h
Time Frame	Up to 48 weeks or until disease progression

Outcome Measure Data

Analysis Population Description

The response-evaluable population is defined as phase 2 patients with measurable disease at baseline and with at least 1 post baseline response assessment.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	41	40	32	17
Number [participants]	21 50%	23 34.8%	13 39.4%	9 52.9%

2. Secondary Outcome

Title	Number of Patients With Adverse Events (AEs)
Description	Evaluate the safety and tolerability of the combination therapy
Time Frame	From first dose of study drug through the 30 day post-treatment AE assessment visit

Outcome Measure Data

Analysis Population Description

The safety population includes patients received any dose of any study drug.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 100 - 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	42	66	33	17
Number [participants]	42 100%	65 98.5%	33 100%	17 100%

3. Secondary Outcome

Title	Number of Patients With Overall Response
Description	Overall Response includes complete response and partial response. Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. Partial response requires at least 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by at least 90% or to < 200 mg per 24 hour.
Time Frame	Up to 48 weeks or until disease progression

Outcome Measure Data

Analysis Population Description

The response-evaluable population is defined as phase 2 patients with measurable disease at baseline and with at least 1 post baseline response assessment.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	41	40	32	17
Number [participants]	35 83.3%	35 53%	24 72.7%	17 100%

4. Secondary Outcome

Title	Number of Patients With Stringent Complete Response Rate
Description	Stringent Complete Response is defined as complete response plus normal free light chain (kappa/lambda) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Time Frame	Up to 48 weeks or until disease progression

Outcome Measure Data

Analysis Population Description

The response-evaluable population is defined as phase 2 patients with measurable disease at baseline and with at least 1 post baseline response assessment.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	41	40	32	17
Number [participants]	7 16.7%	6 9.1%	3 9.1%	5 29.4%

5. Secondary Outcome

Title	Number of Patients With Complete Response Rate + Near Complete Response Rate
Description	Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. Near Complete response requires positive immunofixation on the serum and/or urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow.
Time Frame	Up to 48 weeks or until disease progression

Outcome Measure Data

Analysis Population Description

The response-evaluable population is defined as phase 2 patients with measurable disease at baseline and with at least 1 post baseline response assessment.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	41	40	32	17
Number [participants]	17 40.5%	14 21.2%	10 30.3%	8 47.1%

6. Secondary Outcome

Title	Duration of Response
Description	Duration of response is the time from date of first documented confirmed response to date of first documented progressive disease. A confirmed response is a response that has been observed on at least two consecutive assessments. Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.
Time Frame	Up to 48 weeks or until disease progression

Outcome Measure Data

Analysis Population Description

Responders (patients achieved complete and partial response) in the response evaluable population.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	35	35	24	17
Median (95% Confidence Interval) [days]	NA	NA	NA	NA

7. Secondary Outcome

Title	Time to Disease Progression
Description	Time to disease progression is defined as time from the date of randomization to the date of first documented progressive disease. Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.
Time Frame	Up to 48 weeks or until disease progression

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat population is defined as phase 2 patients received at least one dose of any drug.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	42	48	33	17
Median (95% Confidence Interval) [days]	NA	NA	NA	NA

8. Secondary Outcome

Title	Time to Response
Description	Time to response is defined as time from date of randomization to the date of the first documentation of a confirmed response. confirmed response is a response that has been observed on at least two consecutive assessments.
Time Frame	Up to 48 weeks or until disease response

Outcome Measure Data

Analysis Population Description

Responders (patients achieved complete and partial response) in the response evaluable population.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	35	35	24	17
Median (Full Range) [days]	49	50	55	49

9. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival is defined as time from the date of randomization to the date of the first documented progressive disease or death. Disease progression requires any one or more of the following: serum m-protein increase >= 25% from nadir(absolute increase >= 0.5 g/dL); Urine m-protein increase >= 25% from nadir(absolute increase >= 200 mg/24 hr), bone marrow plasma cell percentage increase >= 25% from nadir(absolute increase >= 10%), new bone lesion or soft tissue plasmacytomas.
Time Frame	Up to 48 weeks or until disease progression/death

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat population is defined as phase 2 patients received at least one dose of any drug.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	42	48	33	17
Median (95% Confidence Interval) [days]	NA	631	NA	NA

10. Secondary Outcome

Title	Probability of 1-year Survival
Time Frame	survival probability at 1 year after randomization

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat population is defined as phase 2 patients received at least one dose of any drug.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	42	48	33	17
Number [percentage of patients]	100	91.6	100	100

11. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as time from the date of randomization to the date of death
Time Frame	Up to 48 weeks or until death

Outcome Measure Data

Analysis Population Description

The modified intent-to-treat population is defined as phase 2 patients received at least one dose of any drug.

Arm/Group Title	V-DR	VDCR	V-DC	VDC-mod
Arm/Group Description	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.	Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
Measure Participants	42	48	33	17
Median (95% Confidence Interval) [days]	NA	NA	NA	NA

Adverse Events

Time Frame	From first dose of any study drug to 30-day post-treatment adverse event assessment, up to 48 weeks and 30 days
Adverse Event Reporting Description	From first dose of any study drug to end of treatment period
Arm/Group Title	V-DR		VDCR		V-DC		VDC-mod
Arm/Group Description	VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally [PO] on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 25 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.		VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide) Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 100 - 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop. Lenalidomide: 15 mg PO on Days 1 through 14 of a 3-week cycle for 8 cycles, then stop.		VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg orally PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1 and 8 of a 3-week cycle for 8 cycles, then stop.		Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide Bortezomib: 1.3 mg/m^2/dose IV on Days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on Days 1, 8, 15, and 22 of a 6-week cycle for 4 cycles. Dexamethasone: 40 mg PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop. Cyclophosphamide: 500 mg/m^2 dose PO on Days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop.
All Cause Mortality
	V-DR		VDCR		V-DC		VDC-mod
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	V-DR		VDCR		V-DC		VDC-mod
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/42 (40.5%)		26/66 (39.4%)		7/33 (21.2%)		7/17 (41.2%)
Blood and lymphatic system disorders
Febrile neutropenia	1/42 (2.4%)		5/66 (7.6%)		0/33 (0%)		0/17 (0%)
Pancytopenia	1/42 (2.4%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Thrombocytopenia	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Anaemia NOS	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Leukopenia NOS	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Cardiac disorders
Acute myocardial infarction	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Angina pectoris	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Angina unstable	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Cardiac failure congestive	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Pulmonary oedema NOS	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Pericarditis NOS	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Atrial fibrillation	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Gastrointestinal disorders
Nausea	1/42 (2.4%)		3/66 (4.5%)		1/33 (3%)		0/17 (0%)
Vomiting NOS	1/42 (2.4%)		3/66 (4.5%)		1/33 (3%)		0/17 (0%)
Small intestinal obstruction NOS	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		1/17 (5.9%)
Abdominal pain NOS	1/42 (2.4%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Diverticular perforation NOS	0/42 (0%)		1/66 (1.5%)		1/33 (3%)		0/17 (0%)
Diarrhoea NOS	0/42 (0%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Antibiotic associated colitis	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Caecitis	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
General disorders
Pyrexia	2/42 (4.8%)		3/66 (4.5%)		1/33 (3%)		1/17 (5.9%)
Fatigue	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Malaise	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Weakness	0/42 (0%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Fall	1/42 (2.4%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Oedema peripheral	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Neuralgia NOS	0/42 (0%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Hepatobiliary disorders
Hypoproteinaemia	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Infections and infestations
Pneumonia NOS	2/42 (4.8%)		3/66 (4.5%)		0/33 (0%)		1/17 (5.9%)
Lobar pneumonia NOS	1/42 (2.4%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Septic shock	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Herpes simplex	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Herpes zoster	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Cellulitis	1/42 (2.4%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Urinary tract infection NOS	0/42 (0%)		0/66 (0%)		2/33 (6.1%)		0/17 (0%)
Respiratory syncytial virus infection NOS	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Arthritis infective NOS	0/42 (0%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Colitis pseudomembranous	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Stye	0/42 (0%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Influenza	0/42 (0%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Pneumonia streptococcal	0/42 (0%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Upper respiratory tract infection NOS	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Bacteraemia	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Injury, poisoning and procedural complications
Haemothorax	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Compression fracture	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Muscle injury NOS	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Subdural haematoma	0/42 (0%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Wound dehiscence	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Investigations
Blood creatinine increased	0/42 (0%)		1/66 (1.5%)		1/33 (3%)		0/17 (0%)
Blood culture positive	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Metabolism and nutrition disorders
Dehydration	1/42 (2.4%)		2/66 (3%)		0/33 (0%)		1/17 (5.9%)
Hypovolaemia	0/42 (0%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Failure to thrive	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Malnutrition NOS	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Hyponatraemia	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Hypocalcaemia	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Hypokalaemia	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/42 (0%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Back pain aggravated	0/42 (0%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Arthralgia	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Pathological fracture	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Myalgia	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Muscle weakness NOS	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Nervous system disorders
Syncope	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		2/17 (11.8%)
Headache NOS	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Convulsions NOS	0/42 (0%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Psychiatric disorders
Confusion	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Agitation	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Renal and urinary disorders
Renal failure NOS	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Renal failure acute	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Renal impairment NOS	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Urinary retention	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Cystitis haemorrhagic	0/42 (0%)		0/66 (0%)		0/33 (0%)		1/17 (5.9%)
Haematuria	0/42 (0%)		0/66 (0%)		1/33 (3%)		0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea NOS	2/42 (4.8%)		2/66 (3%)		0/33 (0%)		0/17 (0%)
Respiratory distress	1/42 (2.4%)		0/66 (0%)		0/33 (0%)		0/17 (0%)
Skin and subcutaneous tissue disorders
Angioneurotic oedema	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Erythema multiforme	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Vascular disorders
Hypotension NOS	1/42 (2.4%)		2/66 (3%)		2/33 (6.1%)		0/17 (0%)
Venous thrombosis deep limb	0/42 (0%)		1/66 (1.5%)		0/33 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	V-DR		VDCR		V-DC		VDC-mod
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/42 (97.6%)		65/66 (98.5%)		33/33 (100%)		17/17 (100%)
Blood and lymphatic system disorders
Neutropenia	8/42 (19%)		33/66 (50%)		17/33 (51.5%)		8/17 (47.1%)
Lymphopenia	5/42 (11.9%)		6/66 (9.1%)		4/33 (12.1%)		0/17 (0%)
Ear and labyrinth disorders
Ear pain	1/42 (2.4%)		3/66 (4.5%)		2/33 (6.1%)		2/17 (11.8%)
Eye disorders
Vision blurred	7/42 (16.7%)		6/66 (9.1%)		4/33 (12.1%)		2/17 (11.8%)
Gastrointestinal disorders
Constipation	26/42 (61.9%)		29/66 (43.9%)		16/33 (48.5%)		7/17 (41.2%)
Gastro-oesophageal reflux disease	2/42 (4.8%)		6/66 (9.1%)		3/33 (9.1%)		1/17 (5.9%)
Dyspepsia	3/42 (7.1%)		6/66 (9.1%)		8/33 (24.2%)		3/17 (17.6%)
Abdominal distension	8/42 (19%)		3/66 (4.5%)		1/33 (3%)		4/17 (23.5%)
Flatulence	2/42 (4.8%)		4/66 (6.1%)		1/33 (3%)		1/17 (5.9%)
Hiccups	3/42 (7.1%)		6/66 (9.1%)		1/33 (3%)		0/17 (0%)
Stomatitis	1/42 (2.4%)		6/66 (9.1%)		1/33 (3%)		0/17 (0%)
Mouth ulceration	2/42 (4.8%)		3/66 (4.5%)		2/33 (6.1%)		0/17 (0%)
Pharyngolaryngeal pain	3/42 (7.1%)		6/66 (9.1%)		1/33 (3%)		2/17 (11.8%)
Abdominal pain upper	3/42 (7.1%)		4/66 (6.1%)		1/33 (3%)		1/17 (5.9%)
Day mouth	3/42 (7.1%)		4/66 (6.1%)		0/33 (0%)		1/17 (5.9%)
General disorders
Oedema lower limb	9/42 (21.4%)		19/66 (28.8%)		8/33 (24.2%)		5/17 (29.4%)
Rigors	11/42 (26.2%)		14/66 (21.2%)		5/33 (15.2%)		2/17 (11.8%)
Pain NOS	6/42 (14.3%)		7/66 (10.6%)		2/33 (6.1%)		0/17 (0%)
Infections and infestations
Nasopharyngitis	4/42 (9.5%)		8/66 (12.1%)		4/33 (12.1%)		2/17 (11.8%)
Investigations
Weight decreased	3/42 (7.1%)		5/66 (7.6%)		6/33 (18.2%)		1/17 (5.9%)
Alanine aminotransferase increased	4/42 (9.5%)		1/66 (1.5%)		4/33 (12.1%)		2/17 (11.8%)
Aspartate aminotransferase increased	3/42 (7.1%)		1/66 (1.5%)		3/33 (9.1%)		2/17 (11.8%)
Haemoglobin decreased	1/42 (2.4%)		2/66 (3%)		4/33 (12.1%)		3/17 (17.6%)
Metabolism and nutrition disorders
Anorexia	4/42 (9.5%)		15/66 (22.7%)		5/33 (15.2%)		2/17 (11.8%)
Appetite decreased NOS	6/42 (14.3%)		5/66 (7.6%)		1/33 (3%)		2/17 (11.8%)
Hypophosphataemia	3/42 (7.1%)		8/66 (12.1%)		4/33 (12.1%)		1/17 (5.9%)
Hyperglycaemia NOS	6/42 (14.3%)		4/66 (6.1%)		5/33 (15.2%)		1/17 (5.9%)
Hypomagnesaemia	2/42 (4.8%)		4/66 (6.1%)		2/33 (6.1%)		2/17 (11.8%)
Musculoskeletal and connective tissue disorders
Pain in limb	12/42 (28.6%)		22/66 (33.3%)		12/33 (36.4%)		7/17 (41.2%)
Bone pain	4/42 (9.5%)		6/66 (9.1%)		3/33 (9.1%)		1/17 (5.9%)
Muscle cramps	7/42 (16.7%)		9/66 (13.6%)		2/33 (6.1%)		2/17 (11.8%)
Nervous system disorders
Peripheral neuropathy NOS	14/42 (33.3%)		24/66 (36.4%)		15/33 (45.5%)		9/17 (52.9%)
Peripheral sensory neuropathy	17/42 (40.5%)		26/66 (39.4%)		9/33 (27.3%)		1/17 (5.9%)
Dizziness (excl vertigo)	13/42 (31%)		18/66 (27.3%)		4/33 (12.1%)		3/17 (17.6%)
Dysgeusia	8/42 (19%)		9/66 (13.6%)		3/33 (9.1%)		1/17 (5.9%)
Paraesthesia	4/42 (9.5%)		6/66 (9.1%)		2/33 (6.1%)		2/17 (11.8%)
Hypoaesthesia	2/42 (4.8%)		5/66 (7.6%)		4/33 (12.1%)		0/17 (0%)
Tremor	5/42 (11.9%)		5/66 (7.6%)		1/33 (3%)		1/17 (5.9%)
Psychiatric disorders
Insomnia	14/42 (33.3%)		21/66 (31.8%)		9/33 (27.3%)		6/17 (35.3%)
Anxiety NEC	4/42 (9.5%)		10/66 (15.2%)		1/33 (3%)		1/17 (5.9%)
Depression NOS	1/42 (2.4%)		7/66 (10.6%)		1/33 (3%)		1/17 (5.9%)
Weight increased	1/42 (2.4%)		3/66 (4.5%)		4/33 (12.1%)		1/17 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	16/42 (38.1%)		14/66 (21.2%)		5/33 (15.2%)		2/17 (11.8%)
Dyspnoea exertional	5/42 (11.9%)		5/66 (7.6%)		3/33 (9.1%)		2/17 (11.8%)
Hoarseness	2/42 (4.8%)		4/66 (6.1%)		1/33 (3%)		1/17 (5.9%)
Chest wall pain	2/42 (4.8%)		4/66 (6.1%)		5/33 (15.2%)		2/17 (11.8%)
Sinus congestion	4/42 (9.5%)		1/66 (1.5%)		2/33 (6.1%)		1/17 (5.9%)
Skin and subcutaneous tissue disorders
Rash pruritic	7/42 (16.7%)		7/66 (10.6%)		4/33 (12.1%)		0/17 (0%)
Pruritus NOS	5/42 (11.9%)		6/66 (9.1%)		2/33 (6.1%)		2/17 (11.8%)
Night sweats	4/42 (9.5%)		5/66 (7.6%)		1/33 (3%)		2/17 (11.8%)
Sweating increased	3/42 (7.1%)		7/66 (10.6%)		0/33 (0%)		0/17 (0%)
Rash erythematous	5/42 (11.9%)		9/66 (13.6%)		2/33 (6.1%)		1/17 (5.9%)
Rash NOS	1/42 (2.4%)		6/66 (9.1%)		0/33 (0%)		2/17 (11.8%)
Alopecia	3/42 (7.1%)		3/66 (4.5%)		2/33 (6.1%)		1/17 (5.9%)
Dermatitis exfoliative NOS	3/42 (7.1%)		2/66 (3%)		0/33 (0%)		3/17 (17.6%)
Vascular disorders
Flushing	2/42 (4.8%)		5/66 (7.6%)		1/33 (3%)		1/17 (5.9%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.