Phase II Study of Biaxin, Revlimid, and Dexamethasone for Untreated Multiple Myeloma

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.