Lenalidomide, Cyclophosphamide, and Dexamethasone 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)