CC-5013 With or Without Dexamethasone in Treating Patients With Primary Systemic Amyloidosis

Study Overview
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Brief Summary
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RATIONALE: Drugs such as CC-5013 and dexamethasone may be effective in treating primary systemic amyloidosis. PURPOSE: This phase II trial is studying CC-5013 to see how well it works with or without dexamethasone in treating patients with primary systemic amyloidosis.

Detailed Description
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OBJECTIVES: Primary Determine the tolerability of CC-5013 in patients with primary systemic (AL) amyloidosis. Determine the objective hematologic response rate in patients treated with this drug. Determine amyloid organ disease response in patients treated with this drug. Secondary Determine hematologic and amyloid organ disease response in patients who do not achieve a response to CC-5013 alone and are subsequently treated with CC-5013 and dexamethasone. Determine the toxicity of CC-5013 in combination with dexamethasone in these patients. OUTLINE: Patients receive oral CC-5013 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients not achieving a hematologic response continue to receive CC-5013 as before and also receive oral dexamethasone twice daily on days 1-4, 9-12, and 17-20 of every other 28-day course for up to 6 courses of combination therapy. Patients who maintain a hematologic response after 6 courses of combination therapy may receive CC-5013 alone in the absence of disease progression or unacceptable toxicity. Patients not achieving a hematologic response after the initiation of dexamethasone are removed from the study. Patients are followed annually. PROJECTED ACCRUAL: A total of 15-25 patients will be accrued for this study within 5-12.5 months.

Official Title
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A Phase II Trial of the Immunomodulatory Drug CC-5013 for Patients With AL Amyloidosis

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: dexamethasone
* Drug: lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DISEASE CHARACTERISTICS: Histologically confirmed primary systemic (AL) amyloidosis Tissue amyloid deposits or positive fat aspirate Meets 1 of the following criteria for AL type disease: Serum or urine monoclonal protein by immunofixation electrophoresis Plasmacytosis of bone marrow by monoclonal staining for kappa- or lambda-light chain isotype PATIENT CHARACTERISTICS: Age 18 and over Performance status SWOG 0-2 Life expectancy Not specified Hematopoietic White blood count> 3,000/mm^3 Hemoglobin > 8 g/dL Platelet count > 100,000/mm^3 Absolute neutrophil count > 1,000/mm^3 Hepatic Bilirubin ≤ 2 times upper limit of normal (ULN) aspartate aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 times ULN PRIOR CONCURRENT THERAPY: Biologic therapy Prior thalidomide for AL amyloidosis allowed Chemotherapy More than 4 weeks since prior cytotoxic chemotherapy Endocrine therapy Prior steroids for AL amyloidosis allowed Radiotherapy More than 4 weeks since prior radiotherapy Surgery Prior surgery allowed Other Recovered from all prior therapy Exclusion Criteria: No secondary or familial amyloidosis No multiple myeloma, defined as ≥ 30% plasma cells in bone marrow biopsy specimen OR lytic bone lesions No prior CC-5013 Renal No dialysis Cardiovascular No symptomatic cardiac arrhythmia No oxygen-dependent restrictive cardiomyopathy Other No untreated or uncontrolled infection No other malignancy except basal cell skin cancer or carcinoma in situ of the cervix or breast No other serious medical illness that would preclude study participation No history of hypersensitivity reaction to thalidomide HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: revlimid<br>lenalidomide 15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone 20 mg daily (10 mg BID) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle. | Drug: dexamethasone<br>* dexamethasone 20 mg daily (10 mg BID) on Days 1-4, 9-12, and 17-20 of every other 28-day cycle.<br>* Other names: dexamethasone acetate;Drug: lenalidomide<br>* 15 mg/day, for 21 days with 7 days rest (28 day cycle) with or without dexamethasone<br>* Other names: revlimid; CC-5013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Removed From Study Treatment Due to Toxicities |  | 1 year | 
| Number of Patients With Hematologic Response With Single-agent CC-5013 | Complete response = Absence of detectable monoclonal protein in serum or urine by immunofixation electrophoresis, less than 5% plasma cells on bone marrow biopsy without clonal dominance of kappa or lambda isotype, and normal serum free light chain assay. Partial response= For patients with detectable and quantifiable monoclonal marrow plasmacytosis= a reduction of 50% or more in plasma cells as a percentage of nucleated bone marrow cells. For patients with a detectable monoclonal peak on serum or urine protein electrophoresis= a reduction in the peak height of 50% or more. For patients with quantifiable urinary kappa or lambda chain concentration= a 50% reduction in daily light chain excretion in 24 hour urine. For patients with an elevated serum free light chain assay, a reduction of 50% or more. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Who Received Both CC-5013 and Dexamethasone and Had a Hematologic Response |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary systemic amyloidosis