Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65

After screening procedures determine if a patient is eligible for this research study, the
patient will be randomized into one of the study groups: lenalidomide, bortezomib and
dexamethasone without autologous stem cell transplantation, followed by lenalidomide
maintenance (Arm A) or lenalidomide, bortezomib and dexamethasone with autologous stem cell
transplantation, followed by lenalidomide maintenance (Arm B). There is an equal chance of
being placed in either group.

All participants will receive one cycle of lenalidomide, bortezomib and dexamethasone
treatment before being randomized to Arm A or Arm B.

Participants in Arm A will receive two additional cycles of lenalidomide, bortezomib and
dexamethasone prior to stem cell collection. If randomized to Arm A, the subject will undergo
stem cell collection, followed by five cycles of lenalidomide, bortezomib and dexamethasone.
This will be followed by lenalidomide maintenance treatment until disease progression.

Participants in Arm B will receive two additional cycles of lenalidomide, bortezomib and
dexamethasone prior to stem cell collection. If randomized to Arm B, the subject will undergo
stem cell collection and autologous stem cell transplantation, followed by two cycles of
lenalidomide, bortezomib and dexamethasone. This will be followed by lenalidomide maintenance
treatment until disease progression.

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 at least 7 days
before study entry, corticosteroids allowed if dose dexamethasone 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. If malignancy was experienced more than 2 years ago and
confirmed as cured, these participants may be considered for the study on case by case
basis with PI discussion.

- Inability to comply with an anti-thrombotic treatment regimen

- Peripheral neuropathy >/= Grade 2