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

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

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.

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.

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