• Progression-free survival [ Designated as safety issue: No ]
  

• Overall response rates [ Designated as safety issue: No ]
  
• Major response rate as measured by a decrease in m-protein > 75% [ Designated as safety issue: No ]
  
• Time to best response [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Toxicity as measured by CTCAE v. 3.0 [ Designated as safety issue: Yes ]
  
• Biological endpoints including effects on gene expression and proteomic analysis at baseline and after 3 courses of treatment [ Designated as safety issue: No ]
  

OBJECTIVES:

• Compare the progression-free survival of patients with previously untreated stage I, II, or III multiple myeloma treated with dexamethasone with or without lenalidomide.
• Compare the overall response rate in patients treated with these regimens.
• Compare the major response rate (indicated by greater than 75% decrease in M-protein) in patients treated with these regimens.
• Compare the overall survival and time to best response in patients treated with these regimens.
• Compare the toxicity profile of these regimens, including thrombotic complications, in these patients.
• Compare the effect of these regimens on gene expression and proteomic analysis in these patients.

OUTLINE: This is a randomized, double-blind, crossover, multicenter study. Patients are stratified according to disease stage by the International Staging System (I vs II vs III) and Zubrod performance status (0-1 vs 2-3). Patients are randomized to 1 of 2 treatment arms.

Arm I

• Induction therapy: Patients receive oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
• Maintenance therapy: Patients receive oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Arm II

• Induction therapy: Patients receive DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction.

Patients with responding or stable disease proceed to maintenance therapy. Patients with disease progression during induction therapy cross over and receive unblinded treatment with DM and lenalidomide as in arm I induction. Patients with responding or stable disease after unblinded induction therapy receive unblinded maintenance therapy with DM and lenalidomide as in arm I maintenance.

• Maintenance therapy: Patients receive oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.

Patients with disease progression during maintenance therapy cross over and receive unblinded treatment with DM and lenalidomide as in arm I induction. Patients with responding or stable disease after unblinded induction therapy proceed to unblinded maintenance therapy with DM and lenalidomide as in arm I maintenance.

Patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this study within 4 years.

DISEASE CHARACTERISTICS:

• Previously untreated multiple myeloma

  • Stage I, II, or III disease by the International Staging System

• Measurable M-protein as defined by 1 of the following:

  • Serum M-protein at least 1.0 g/dL by serum protein electrophoresis or immunoelectrophoresis
  • Urinary M-protein excretion at least 200 mg/24 hours
• No nonsecretory multiple myeloma
• Not planning to undergo future autologous stem cell transplantation

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-3* NOTE: *Zubrod 3 allowed only if multiple myeloma is the central cause of disability

Life expectancy

• Not specified

Hematopoietic

• Platelet count at least 80,000/mm^3*
• Absolute neutrophil count at least 1,000/mm^3*
• Hemoglobin at least 9 g/dL* (epoetin alfa or transfusion allowed) NOTE: *Unless due to greater than 50% marrow involvement by myeloma on biopsy

Hepatic

• AST/ALT no greater than 3 times upper limit of normal* NOTE: *Values outside of this range are allowed at the investigator's discretion

Renal

• Creatinine no greater than 2.5 mg/dL* NOTE: *Values outside of this range are allowed at the investigator's discretion

Cardiovascular

• No New York Heart Association class III or IV heart failure
• No myocardial infarction within the past 6 months
• No poorly controlled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test

• Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment

  • Female patients must use 2 reliable forms of contraception simultaneously
  • Male patients must use effective barrier contraception
• No uncontrolled active infection requiring IV antibiotics
• No poorly controlled diabetes mellitus that would preclude ability to take oral glucocorticoids
• No other serious medical condition that would preclude study participation
• No psychiatric illness that would preclude study participation
• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• Must be able to take aspirin by mouth at a dose of 325 mg per day or enoxaparin subcutaneously at a dose of 40 mg per day as a form of thrombotic prophylaxis, except if already on therapeutic anticoagulant medication

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior interferon or thalidomide

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior high-dose dexamethasone allowed provided duration of administration was no more than 4 days

Radiotherapy

• Prior localized radiotherapy allowed provided it was not to the sole site of evaluable disease

Surgery

• Not specified

Other

• No prior treatment for clinically significant ventricular cardiac arrhythmias
• Concurrent bisphosphonates allowed