RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop plasma cells from growing. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may be an effective treatment for primary systemic amyloidosis.

PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with primary systemic amyloidosis.

OBJECTIVES:

Primary

* Assess the hematologic response rate in patients with primary systemic amyloidosis treated with lenalidomide, cyclophosphamide, and dexamethasone.

Secondary

• Determine the organ response rate in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the time to progression in patients treated with this regimen.
• Determine the survival of patients treated with this regimen.

OUTLINE: Patients receive oral lenalidomide on days 1-21, oral cyclophosphamide* on days 1, 8, and 15, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients may receive cyclophosphamide for up to 1 year. After completion of study treatment, patients are followed every 6 months for up to 3 years.

DISEASE CHARACTERISTICS:

• Histochemical diagnosis of AL amyloidosis based on detection of green birefringent material in Congo red-stained tissue specimens by polarizing microscopy

• Measurable disease, as defined by one of the following:

  • Serum monoclonal protein ≥ 1.0 g by serum electrophoresis
  • Urine monoclonal protein > 200 mg by 24-hour urine electrophoresis
  • Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio

• Symptomatic organ involvement with amyloid to justify therapy

  • May include liver involvement, cardiac involvement, renal involvement, grade 1 peripheral neuropathy, or soft tissue involvement
  • Must have more than skin purpura or carpal tunnel syndrome

• No amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as only evidence of disease

  - Vascular amyloid only in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis

• No clinically overt multiple myeloma (i.e., monoclonal BMPC > 30%, bone lesions, or hypercalcemia)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,000/μL
• Platelet count ≥ 75,000/μL
• Creatinine < 3.0 mg/dL
• Not pregnant
• Negative pregnancy test
• Fertile patients must use two acceptable methods of contraception for ≥ 28 days prior to, during, and for ≥ 28 days after completion of study treatment
• No nursing during and for ≥ 28 days after completion of study treatment
• No blood, semen, or sperm donation during and for ≥ 28 days after completion of study treatment
• No malignancies within the past 5 years except treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
• No neuropathy ≥ grade 2, defined as motor neuropathy (symptomatic weakness interfering with function, but not interfering with activities of daily living [ADL]) or sensory neuropathy (sensory alteration or paresthesia [including tingling], interfering with function, but not interfering with ADL)
• No uncontrolled infection
• No syncope within the past 30 days
• No known hypersensitivity to thalidomide, including desquamating rash with thalidomide in the past
• No known seropositivity for HIV
• No active hepatitis A, B, or C
• No New York Heart Association class III or IV heart disease
• No venous thromboembolic event within the past 42 days
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation - Patients intolerant to aspirin may use low molecular weight heparin

PRIOR CONCURRENT THERAPY:

• No prior lenalidomide
• More than 2 weeks since prior and no other concurrent anticancer agents or treatments
• More than 4 weeks since prior experimental agents
• No other concurrent corticosteroids except chronic steroids (maximum dose 20 mg/day of prednisone equivalent) for disorders other than amyloidosis (e.g., adrenal insufficiency or rheumatoid arthritis)