An Intergroup Phase III Randomized Controlled Trial Comparing Melphalan, Prednisone and Thalidomide (MPT) Versus Melphalan, Prednisone and Lenalidomide (Revlimid™) (MPR) in Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for High-Dose Therapy

Inclusion Criteria:

- Newly diagnosed multiple myeloma (MM), meeting the following criteria:

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

- Symptomatic disease with evidence of end-organ damage at initial diagnosis that
prompted the initiation of therapy, including ≥ 1 of the following:

- Anemia

- Hypercalcemia

- Bone disease (lytic bone lesions or pathologic fracture)

- Renal dysfunction

- No smoldering MM, defined by all of the following:

- Serum monoclonal protein ≥ 3 g/dL

- Bone marrow plasma cells ≥ 10% or greater

- Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction

- No monoclonal gammopathy of undetermined significance, defined by all of the
following:

- Serum monoclonal protein < 3 g/dL

- Bone marrow plasma cells ≤ 10%

- Absence of anemia, hypercalcemia, lytic bone lesions, or renal dysfunction

- Previously untreated for MM

- Patients 18 to 64 years old must not be a candidate for autologous stem cell
transplantation or have declined transplantation or other alternative treatment

- ECOG performance status 0-2

- Hemoglobin > 7 g/dL

- Platelet count > 75,000/mm³

- ANC > 1,000/mm³

- 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

- No uncontrolled intercurrent illness that would limit compliance with the study
including, but not limited to, any of the following:

- Uncontrolled hypertension

- Symptomatic congestive heart failure

- Unstable angina

- Uncontrolled cardiac arrhythmia

- Uncontrolled psychiatric illness or social situation

- Prior history of Stevens Johnson syndrome

- No peripheral neuropathy ≥ grade 2

- No active uncontrolled infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-barrier contraception 4 weeks prior to,
during, and 4 weeks after completion of study treatment

- Must be able to take prophylactic aspirin 325mg/day or low-molecular weight heparin
or Coumadin

- No second active malignancy requiring treatment within the past 2 years, except for
basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix

- Concurrent localized radiation therapy is allowed for pain control at the physician's
discretion

- No prior treatment for myeloma except for either of the following:

- Prednisone or dexamethasone treatment for myeloma for a duration of less than 4
weeks

- Prednisone or dexamethasone in combination with thalidomide or lenalidomide for
a duration of less than 2 weeks total

- Concurrent bisphosphonates or growth factors (i.e., erythropoietin) for MM allowed