Melphalan, Thalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed, Previously Untreated Primary Systemic Amyloidosis

Study Overview
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Brief Summary
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RATIONALE: Drugs such as melphalan, thalidomide, and dexamethasone may be effective in treating patients with primary systemic amyloidosis. PURPOSE: This phase II trial is studying how well giving melphalan together with thalidomide and dexamethasone works in treating patients with primary systemic amyloidosis.

Detailed Description
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OBJECTIVES: Primary Determine the 2-year and overall progression-free survival of patients with newly diagnosed, previously untreated primary systemic (AL) amyloidosis treated with risk-adapted melphalan followed by thalidomide and dexamethasone. Secondary Determine plasma cell disease response in these patients at 3, 12, and 24 months after treatment with this regimen. Determine amyloid-related disease response in these patients at 12 and 24 months after treatment with this regimen. Determine the prognostic significance of immunoglobulin light-chain variable-region germline gene expression by AL plasma cell clones in patients treated with this regimen. Determine whether there is molecular minimal residual disease at 12 and 24 months in patients achieving a complete hematologic response after treatment with this regimen. OUTLINE: Patients are stratified according to the extent of amyloid-related disease (low-risk vs high-risk). High-risk disease: Patients receive 2 courses of low-dose melphalan IV, dexamethasone, and filgrastim (G-CSF). After 3 months, patients receive thalidomide and dexamethasone if plasma cell disease persists. Low-risk disease: Patients receive 1 course of high-dose melphalan IV and G-CSF. Patients then receive thalidomide and dexamethasone as in high-risk disease regimen. Patients are followed at 3, 12, and 24 months. PROJECTED ACCRUAL: A total of 82 patients will be accrued for this study.

Official Title
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Risk Adapted Intravenous Melphalan and Adjuvant Thalidomide and Dexamethasone for Untreated Patients With Primary Systemic Amyloidosis

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: filgrastim
* Drug: dexamethasone
* Drug: melphalan
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of primary systemic (AL) amyloidosis within the past 12 months High- or low-risk disease, determined by the extent of systemic organ involvement with disease and patient age PATIENT CHARACTERISTICS: Age 18 and over Performance status SWOG 0-3 Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Cardiovascular No New York Heart Association class III or IV congestive heart failure No restrictive cardiomyopathy requiring oxygen No myocardial infarction within the past 6 months No symptomatic cardiac arrhythmia within the past 60 days Other No other active malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I cancer in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for AL amyloidosis Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other No other prior or concurrent therapy for AL amyloidosis

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: filgrastim|nan|
|Drug: dexamethasone|nan|
|Drug: melphalan|nan|
|Drug: thalidomide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall progression-free survival at 2 years |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma cell disease response at 3, 12, and 24 months after treatment |  |  | 
| Amyloid-related disease response at 12 and 24 months after treatment |  |  | 
| Prognostic significance of immunoglobulin light-chain variable-region germline gene expression by AL cell clones |  |  | 
| Molecular minimal residual disease at 12 and 24 months |  |  | 

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