This phase II trial studies lenalidomide, dexamethasone, and clarithromycin in treating patients who have undergone stem cell transplant for multiple myeloma. Biological therapies, such as lenalidomide and clarithromycin, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with dexamethasone and clarithromycin may be an effective treatment for multiple myeloma.

PRIMARY OBJECTIVES:

I. Evaluate the toxicity of the use of lenalidomide/biaxin (clarithromycin)/dexamethasone as maintenance therapy after autologous/syngeneic transplant.

II. Evaluate the median time to disease progression. III. Evaluate survival.

OUTLINE:

Patients receive clarithromycin orally (PO) twice daily (BID) and dexamethasone PO once a week. Treatment with clarithromycin and dexamethasone continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive lenalidomide PO once daily (QD) on days 1-14. Courses with lenalidomide repeat every 21 days in the absence of disease progression or unacceptable toxicity.

NOTE: *After one year of treatment, dexamethasone is tapered for an additional 4 weeks.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

• Any autologous or syngeneic patient who underwent high dose melphalan (>= 140 mg/m^2) therapy/peripheral blood stem cell (PBSC) or bone marrow (BM) rescue for any stage of multiple myeloma and did not participate in another clinical transplant trial which is also evaluating long-term disease free survival or survival
• Platelet count (transfusion independent) > 50,000 cells/mm^3 and absolute granulocyte count > 1500 cells/mm^3 for 5 calendar days after recovery from high dose therapy
• Patients should be between 30 days to 120 days after transplant
• Willingness and ability to comply with Food and Drug Administration (FDA)-mandated REV ASSIST Program, Celgene System for Lenalidomide Education and Prescribing Safety
• Signing a written informed consent form

Exclusion Criteria:

• Karnofsky score less than 70
• A left ventricular ejection fraction less than 45% immediately pre transplant; patients with congestive heart disease with transplant, history of myocardial infarction (MI), or history of coronary artery disease
• Total bilirubin greater than 2 mg/ml (unless history of Gilbert's disease), serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) > 2.5 x upper limit of normal
• Calculated by Cockcroft-Gault formula or measured serum creatinine clearance < 25 ml/minute
• Pregnant and/or lactating females
• Patients who cannot give informed consent
• Patients with untreated systemic infection
• Patients with history prior to transplant of treatment with combination therapy Lenalidomide/Biaxin and steroid without response
• Patients allergic to lenalidomide, biaxin or dexamethasone
• Referring physician not registered with REV ASSIST program or unwilling to oversee the care of the patients on study and comply with the FDA-mandated REV ASSIST Program
• Patients unwilling to practice adequate forms of contraception if clinically indicated until 30 days after stopping therapy; male patients on study need to be consulted to use latex condoms (even if they have had a vasectomy) every time they have sex with a woman who is able to have children while they are being treated and for 30 days after stopping drugs
• Patients with >= grade 3 peripheral neuropathy
• Prior history of uncontrollable side effects to dexamethasone therapy
• A prior history of human immunodeficiency virus (HIV) positivity with pre-transplant evaluation