Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma

Inclusion Criteria:

• Patients must be diagnosed with symptomatic multiple myeloma within the past 90 daysconfirmed by the following:

• Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells orbiopsy proven plasmacytoma which must be obtained within 4 weeks prior torandomization

• Measurable levels of monoclonal protein (M protein): >= 1.0 g/dL on serumprotein electrophoresis or >= 200 mg of monoclonal light chain on a 24 hoururine protein electrophoresis which must be obtained within 4 weeks prior torandomization; both serum protein electrophoresis (SPEP) and urine proteinelectrophoresis (UPEP) are required to be performed within 28 days prior torandomization; please note that if both serum and urine m-components arepresent, both must be followed in order to evaluate response

• Hemoglobin > 7 g/dL

• Platelet count > 75,000 cells/mm^3

• Absolute neutrophil count > 1000 cells/mm^3

• Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) >= 60mL/min

• Bilirubin =< 1.5 mg/dL

• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) andserum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2.5 times the upper limit of normal

• Prior palliative and/or localized radiation therapy is permitted provided at least 4weeks have passed from date of last radiation therapy to date of registration;patients with prior solitary plasmacytoma treated with radiation therapy withcurative intent are eligible if the disease has now progressed to active multiplemyeloma meeting all the eligibility criteria for this protocol

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

• Females of childbearing potential (FCBP) must have a negative serum or urinepregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days and againwithin 24 hours prior to starting cycle 1 of lenalidomide; further, they must eithercommit to continued abstinence from heterosexual intercourse or begin TWO acceptablemethods of birth control: one highly effective method (intrauterine device [IUD],birth control pills, tubal ligation or partner's vasectomy) and one additionaleffective method (condom, diaphragm or cervical cap); FCBP must also agree toongoing pregnancy testing; men must agree to use a latex condom during sexualcontact with a FCBP, even if they have had a successful vasectomy starting 4 weeksprior to and while taking CC5013 or thalidomide and for four weeks afterdiscontinuing this therapy; a FCBP is a sexually mature woman who: has not undergonea hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausalfor at least 24 consecutive months (i.e., has had menses at any time in thepreceding 24 consecutive months); all patients must be counseled by a trainedcounselor every 28 days about pregnancy precautions and risks of fetal exposure

• Patients with a history of prior malignancy are eligible provided there is no activemalignancy and a low expectation of recurrence within 6 months

Exclusion Criteria:

• No prior systemic therapy with the exception of bisphosphonates for multiple myeloma

• Prior glucocorticosteroid therapy for the treatment of multiple myeloma is notpermitted; prior systemic glucocorticosteroid use for the treatment of non-malignantdisorders is permitted; concurrent use after registration on the study should berestricted to the equivalent of prednisone 10 mg per day; prior or concurrenttopical or localized glucocorticosteroid therapy to treat non-malignant comorbiddisorders is permitted

• Patients must not have active, uncontrolled seizure disorder; patients must have hadno seizures in the last 6 months

• Patients must not have uncontrolled intercurrent illness including uncontrolledhypertension, symptomatic congestive heart failure, unstable angina, uncontrolledcardiac arrhythmia, uncontrolled psychiatric illness or social situation that wouldlimit compliance with the study, or a prior history of Stevens Johnson syndrome

• Patients with smoldering myeloma or monoclonal gammopathy of undeterminedsignificance are not eligible

• Patients must not have grade 2 or higher peripheral neuropathy due to other medicalconditions at the time of randomization

• Patients must not have active, uncontrolled infection

• Patients must not have a history of current or previous deep vein thrombosis orpulmonary embolism regardless of whether or not the patient is receivinganticoagulation therapy

• For patients registered prior to activation of Addendum # 6; patients must bewilling and able to take prophylaxis with either aspirin at 325 mg/day oralternative prophylaxis with either low molecular weight heparin or Coumadin

• For patients registered after activation of Addendum # 6; patients entering theexpansion phase of the protocol, which tests anticoagulant prophylaxis, must beable and willing to be randomized between aspirin at 325 mg/day and Coumadin

• Female patients MUST NOT be pregnant or breastfeeding; due to the potentialteratogenic properties of CC 5013, and the known teratogenicity associated withthalidomide, the use of these drugs in this patient population is ABSOLUTELYCONTRAINDICATED