The following criteria is provided for health care professionals.

Inclusion Criteria:

• Calculated creatinine clearance (using Cockcroft-Gault equation) >= 60 mL/min
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 75000/mm^3
• Hemoglobin >= 8.0 g/dL
• Patient must have relapsed and symptomatic multiple myeloma
• Measurable disease of multiple myeloma as defined by at least one of the following:
  • Serum monoclonal protein >= 1.0 g/dL
  • > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
  • Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Patients must have received at least 1 prior regimen
• Provide informed written consent
• Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Willing to provide bone marrow and blood samples for correlative research purposes

Exclusion Criteria:

• Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma
• Patients who have received > 3 prior treatment regimens for multiple myeloma
• Other malignancy requiring active therapy; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
• Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
• Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; Note: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Prior severe skin reaction (toxic epidermal necrosis) with immunomodulating agents
• Major surgery =< 14 days before study registration
• Concurrent medical problems that preclude use of deep vein thrombosis (DVT) prophylaxis with lenalidomide treatment
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction =< 6 months prior to registration
• Known human immunodeficiency virus (HIV) positive
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Known allergy to any of the study medications, their analogues or excipients in the various formulations