Inclusion Criteria:

• Subject must voluntarily sign and understand written informed consent.
• Histologically confirmed Durie-Salomon stage II or III MM (see Appendix II). Stage I MM patients will be eligible if they display poor prognostic factors (ß2M > or = 5.5 mg/L, plasma cell proliferation index > or = 5%, albumin of less then 3.0, and unfavorable cytogenetics).
• Measurable disease as defined by > 1.0 g/dL serum monoclonal protein, >0.1 g/dL serum free light chains, > 0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
• Age > or = 18 years at the time of signing the informed consent form.
• Karnofsky performance status > or = 70% (>60% if due to bony involvement of myeloma (see Appendix V).
• No prior treatment or less than one full course of first-line therapy. Patients may be receiving adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care.
• If the patient is a woman of childbearing age, she must have a negative serum or urine pregnancy test within 7 days of starting study.
• Due to the unknown risk of teratogenic side effects, subjects (women and men) must agree to use effective contraception throughout the duration of the study and for at least 1 month after discontinuation of study drugs.
• Life expectancy > 3 months
• Absolute neutrophil count (ANC)> or = 1000 cells/mm3 (1.0 x 109/L)
• Platelets count > or = 75,000/mm3 (75 x 109/L)
• Serum SGOT/AST < 3.0 x upper limits of normal (ULN)
• Serum SGPT/ALT < 3.0 x upper limits of normal (ULN)
• Serum creatinine < 2.5 mg/dL (221 µmol/L)
• Serum total bilirubin < 2.0 mg/dL (34 µmol/L)

Exclusion Criteria:

• Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine).
• Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ³ 5 years.
• NYHA Class III or IV heart disease. History of active angina, congestive heart disease, or myocardial infarction within 6 months.
• Pregnant or lactating women are ineligible.
• Known HIV positivity
• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
• Known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or thalidomide.
• Prior therapy for the treatment of MM
• History of thromboembolic event or other condition currently requiring anticoagulation with warfarin (Coumadin). Patients whose therapy is changed to heparin are eligible.