Inclusion Criteria:

• Subject must voluntarily sign and understand written informed consent.
• Age > 18 years at the time of signing the consent form.
• Histologically confirmed Salmon-Durie stage II or III MM. Stage I MM patients will be eligible if they display poor prognostic factors (ß2M ≥5.5 mg/L, plasma cell proliferation index ≥5%, albumin of less then 3.0, and unfavorable cytogenetics).
• Newly diagnosed myeloma.
• No anti-myeloma therapy within 14 days prior to initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may be receiving adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care.
• 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).
• Karnofsky performance status ≥70% (>60% if due to bony involvement of myeloma.
• Able to take aspirin daily as prophylactic anticoagulation. (patients intolerant to ASA may use warfarin or low molecular weight heparin)
• All study participants must be registered into the mandatory RevAssist® and S.T.E.P.S.® programs, and be willing and able to comply with the requirements of RevAssist® and the S.T.E.P.S.® programs.
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide and thalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
• Life expectancy ≥ 3 months

• Subjects must meet the following laboratory parameters:

  • Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L)
  • Platelets count ≥ 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 ≥ 5 years.
• Myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Pregnant or lactating females are ineligible.
• Given the potential of the study drugs to trigger or worsen HIV viremia and the incidence of opportunistic infections inpatients infected with the HIV virus, HIV-1 or HIV-2 positive patients will be excluded. The interactions of HAART with study drugs have not been determined.
• Active hepatitis B or hepatitis C infection.
• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
• Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial.
• Known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or thalidomide.
• History of thromboembolic event within the past 6 months prior to enrollment.