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

Inclusion Criteria:

- Diagnosis of symptomatic multiple myeloma

- Must meet the following criteria at one point in the course of the disease for the
original diagnosis of myeloma:

- Bone marrow plasmacytosis with > 10% plasma cells or sheets of plasma cells or
biopsy proven plasmacytoma

- Must have symptomatic disease that prompted the initiation of therapy (e.g.,
anemia, hypercalcemia, bone disease, or renal dysfunction)

- Must have completed a minimum of 1 and a maximum of 6 courses of a
dexamethasone-based regimen within the past 8 weeks, including any of the following:

- 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

- Cyclophosphamide, lenalidomide, and dexamethasone

- Received a minimum cumulative dose of 160 mg of dexamethasone (no maximum dose
specified)

- Must have not experienced progressive disease on the dexamethasone-based regimen

- Patients diagnosed with only smoldering myeloma or monoclonal gammopathy of
undetermined significance are not eligible

- ECOG performance status 0-2

- Hemoglobin > 7 g/dL

- Platelet count > 75,000/mm^3

- Absolute neutrophil count > 1,000/mm^3 (without the use of growth factors to increase
ANC)

- Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) ≥ 60 mL/min

- Direct bilirubin < 1.5 mg/dL

- ALT and AST < 2.5 times upper limit of normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception for 4 weeks prior to,
during, and for 4 weeks after completion of study therapy

- No active uncontrolled seizure disorder

- No seizure within the past 6 months

- No concurrent uncontrolled illness that would limit compliance with the study,
including any of the following:

- Uncontrolled hypertension

- Symptomatic congestive heart failure

- Unstable angina

- Uncontrolled cardiac arrhythmia

- Uncontrolled psychiatric illness or social situation

- History of Steven Johnson syndrome

- No peripheral neuropathy ≥ grade 2

- No active uncontrolled infection

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

- Must be willing and able to receive prophylaxis with aspirin (325 mg/day) or
alternative prophylaxis with low molecular weight heparin or coumadin

- Patients with prior DVT are eligible provided they remain on the anticoagulation
regimen that was prescribed for treatment of the DVT throughout study therapy

- Concurrent bisphosphonates or growth factors (e.g., granulocyte and/or erythropoietic
agents) for multiple myeloma allowed

- At least 14 days since prior palliative and/or localized radiotherapy

- Prior bortezomib allowed