A Randomized, Phase III Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib, and Dexamethasone (RVD) to High-Dose Treatment With Peripheral Stem Cell Transplant in the Initial Management of Myeloma in Patients Up to 65 Years of Age

Inclusion Criteria:

- Diagnosis of Multiple Myeloma, according to the International Myeloma Foundation 2003
Diagnostic Criteria

- Documented symptomatic myeloma, with organ damage related to myeloma with laboratory
assessments performed within 21 days of registration

- Myeloma that is measurable by either serum or urine evaluation of the monoclonal
component or by assay of serum free light chains.

- ECOG performance status
- Negative HIV blood test

- Voluntary written informed consent

Exclusion Criteria:

- Pregnant or lactating female

- Prior systemic therapy for MM (localized radiotherapy allowed if >/= 2 weeks before
study entry, corticosteroids allowed if dose over 2 weeks)

- Primary amyloidosis (AL) or myeloma complicated by amylosis

- Receiving any other investigational agents

- Known brain metastases

- Poor tolerability or allergy to any of the study drugs or compounds of similar
composition

- Platelet count <50,000/mm3, within 21 days of registration

- ANC <1,000 cells/mm3, within 21 days of registration

- Hemoglobin <8 g/dL, within 21 days of registration

- Hepatic impairment (>/= 1.5 x institutional ULN or AST (SGOT), ALT (SGPT), or
alkaline phosphatase >2 x ULN). Patients with benign hyperbilirubinemia are eligible.

- Renal insufficiency (serum creatinine >2.0 mg/dl or creatinine clearance <50 ml/min,
within 21 days of registration)

- Respiratory compromise (DLCO < 50%)

- Clinical signs of heart or coronary failure or LVEF < 40%. Myocardial infarction
within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
of acute ischemia or active conductive system abnormalities

- Intercurrent illness including, but not limited to ongoing or active severe
infection, known infection with hepatitis B or C virus, poorly controlled diabetes,
severe uncontrolled psychiatric disorder or psychiatric illness/social situations
that would limit compliance with study requirements

- Previous history of another malignant condition except for basal cell carcinoma and
stage I cervical cancer

- Inability to comply with an anti-thrombotic treatment regimen

- Peripheral neuropathy >/= Grade 2