S9628 Dexamethasone Plus Interferon Alfa in Treating Patients With Primary Systemic Amyloidosis

Phase II Study of Dexamethasone/Alpha-Interferon in AL Amyloidosis

RATIONALE: Chemotherapy plus interferon alfa may be effective for primary systemic amyloidosis.

PURPOSE: Phase II trial to study the effectiveness of dexamethasone plus interferon alfa in treating patients who have primary systemic amyloidosis.

OBJECTIVES:

• Evaluate M protein and organ dysfunction responses and overall and progression-free survival in patients with primary systemic amyloidosis treated with dexamethasone/interferon alfa.
• Identify prognostic factors that may relate to response and overall survival in these patients.
• Evaluate the qualitative and quantitative toxic effects of this regimen.

OUTLINE: Patients are stratified by prior amyloidosis treatment (yes vs no).

All patients receive induction therapy with oral dexamethasone on days 1-4, 9-12, and 17-20 every 35 days for a total of 3 courses.

Maintenance therapy begins within 5-8 weeks (within 10 weeks if patients undergo stem cell harvest) of initiation of the third course of induction, as follows: oral dexamethasone for 4 days every 4 weeks; and subcutaneous interferon alfa 3 times per week. Patients who achieved less than a 50% reduction in serum M protein or urinary Bence-Jones protein and who experienced less than grade 3 toxicity during induction receive 3 additional courses of pulse dexamethasone concurrently with entry to maintenance therapy and the initiation of interferon alfa.

Combination therapy is continued until 2 years from entry; thereafter, interferon is administered alone for at least 3 years, toxicity permitting. Patients with stable disease after 5 years of therapy may discontinue interferon alfa at the discretion of the treating physician.

Patients are followed every 6 months for 2 years and yearly thereafter.

PROJECTED ACCRUAL: A total of 100 patients (50 with prior melphalan/prednisone or iododoxorubicin treatment and 50 without) will be entered over 3 years.

DISEASE CHARACTERISTICS:

• Histologically diagnosed primary systemic amyloidosis based on the following:

  • Deposition of fibrillary protein with Congo red positive stain or characteristic electron microscopic appearance

  • Monoclonal light chain protein (Bence-Jones protein) in serum or urine or immunohistochemical studies

  • Evidence of tissue involvement other than carpal tunnel syndrome

  • Diagnostic histologic material available for central pathology review

    • Confirmation of tissue diagnosis at all sites of organ dysfunction encouraged

• No senile, secondary, localized, dialysis-related, or familial amyloidosis

• No known therapy-related myelodysplasia

PATIENT CHARACTERISTICS:

Age:

• Adult

Performance status:

• SWOG 0-4

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No NYHA class IV status

Other:

• No uncontrolled diabetes
• No active peptic ulcer disease
• No medical condition that precludes high-dose steroids
• No second malignancy within 5 years except:
• Adequately treated nonmelanomatous skin cancer
• In situ cervical cancer
• Adequately treated stage I/II cancer in complete remission
• Not pregnant or nursing
• Effective contraception required of fertile patients
• Blood/body fluid analyses within 14 days prior to registration
• Imaging/exams for tumor measurement within 28 days prior to registration
• Other screening exams within 42 days prior to registration

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior interferon alfa

Chemotherapy

• Prior melphalan allowed, but recovered from effects
• At least 4 weeks since cytotoxic therapy and recovered

Endocrine therapy

• Prior prednisone allowed, but recovered from effects
• At least 4 weeks since prior glucocorticoids
• No prior dexamethasone
• No planned or concurrent dexamethasone or other therapy for primary systemic amyloidosis

Radiotherapy

• Not specified

Surgery

• Not specified