Randomized Phase III Trial of Lenalidomide Versus Observation Alone in Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma

Inclusion Criteria:

- Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma
(SMM) within the past 12 months, as confirmed by both of the following:

- Bone marrow plasmacytosis with >= 10% plasma cells or sheet of plasma cells
which must be obtained by bone marrow aspiration and/or biopsy within 4 weeks
prior to randomization

- Abnormal serum free-light chain (FLC) ratio (< 0.125 or > 8.0) by serum FLC
assay; FLC assay must be performed within 28 days of randomization

- Measurable monoclonal protein in the serum >= 1.0 g/dL or urine >= 200 mg/24 hrs

- No lytic lesions on skeletal surveys and no hypercalcemia (i.e., >= 11 mg/dL)

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Absolute neutrophil count (ANC) > 1,500/mm³

- Platelet count > 100,000/mm³

- Hemoglobin > 11 g/dL

- Creatinine clearance > 30 mL/min

- Bilirubin < 1.5 mg/dL

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times upper
limit of normal

- More than 6 months since active, uncontrolled seizure disorder

- Willing to take some form of anti-coagulation as prophylaxis if there is a history of
or concurrent deep vein thrombosis or pulmonary embolism

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 2 effective methods of contraception for ≥ 28 days before,
during, and ≥ 28 days after completion of study therapy

- Prior malignancy allowed provided treatment of curative intent was delivered and
disease-free for time period considered appropriate for the specific cancer

- Human immunodeficiency virus (HIV)-positive patients allowed provided the following
criteria are met:

- CD4 cell count >= 350/mm³

- No history of acquired immunodeficiency syndrome (AIDS)-related illness

- No uncontrolled intercurrent illness including any of the following:

- Uncontrolled hypertension

- Symptomatic congestive heart failure

- Unstable angina

- Uncontrolled cardiac arrhythmia

- Uncontrolled psychiatric illness or social situation that would limit compliance
with the study

- Prior Stevens Johnson Syndrome

- No peripheral neuropathy >= grade 2

- No active uncontrolled infection

- No New York Heart Association (NYHA) class III or IV heart failure

- No prior or concurrent systemic therapy or radiotherapy for MM

- No prior or concurrent erythropoietin

- No prior glucocorticosteroid for MM

- Prior systemic glucocorticosteroid for non-malignant disorders allowed
(prednisone equivalent ≤ 10 mg/day)

- Prior or concurrent topical or localized glucocorticosteroid to treat
non-malignant comorbid disorders allowed

- No concurrent bisphosphonates

- Prior bisphosphonates or once-a-year intravenous bisphosphonate for osteoporosis
allowed

- No concurrent zidovudine or stavudine for HIV-positive patients

- No concurrent chemotherapy including cyclophosphamide and stem cell mobilization