RATIONALE: Iododoxorubicin may dissolve protein deposits and be an effective treatment for primary systemic amyloidosis.

PURPOSE: Phase I trial to determine the effectiveness of iododoxorubicin in treating patients who have primary systemic amyloidosis.

OBJECTIVES:

• Determine the maximum tolerated dose of iododoxorubicin in patients with primary systemic amyloidosis.
• Determine the safety, especially cardiac safety, of this drug in these patients.
• Determine the survival rate of patients treated with this drug.
• Determine, preliminarily, the clinical efficacy of this drug in these patients.
• Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive iododoxorubicin IV over 15 minutes on days 1, 8, 15, and 22. Treatment repeats every 12 weeks for a total of 4 courses or a cumulative dose of 400 mg/m^2 in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of iododoxorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 months.

PROJECTED ACCRUAL: A total of 9-22 patients will be accrued for this study within 12 months.

DISEASE CHARACTERISTICS:

• Histochemically confirmed amyloidosis by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens

• At least one of the following:

  • Demonstrable M-protein in serum or urine
  • Clonal population of plasma cells in bone marrow
  • Immunohistochemical stain with anti-light chain antisera of amyloid fibrils

• Symptomatic organ involvement, including liver involvement, mild cardiac involvement, renal involvement, grade 1 or 2 peripheral neuropathy, or soft tissue involvement (including tongue)

  • No purpura or carpal tunnel syndrome as sole manifestation of disease

• No clinically overt multiple myeloma defined as monoclonal bone marrow platelet concentration greater than 20% and at least one of the following:

  • Bone lesions
  • Anemia
  • Hypercalcemia

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-3 (3 allowed only if related to muscular infiltration by amyloid or peripheral neuropathy)

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3

Hepatic:

• Total bilirubin no greater than 2.0 mg/dL OR
• Direct bilirubin no greater than 1.0 mg/dL
• Alkaline phosphatase no greater than 4 times upper limit of normal (ULN)
• AST or ALT no greater than 3 times ULN

Renal:

• Creatinine clearance at least 40 mL/min

Cardiovascular:

• Ejection fraction at least 50% by echocardiogram
• No New York Heart Association class III or IV heart disease
• No enzyme-documented myocardial infarction within the past 3 years
• No chronic atrial fibrillation
• No grade 2 or 3 atrioventricular block (Mobitz type I allowed)
• No sustained (greater than 30 seconds) ventricular tachycardia, more than 1 episode of non-sustained ventricular tachycardia (3 consecutive ventricular beats), or frequent (more than 20 in 24 hours) ventricular pairs by 24-hour ambulatory electrocardiographic monitoring
• No intraventricular septum greater than 16 mm by echocardiogram

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection
• No other active malignancy except nonmelanoma skin cancer or cervical cancer
• No psychiatric illness or social situation that would preclude study
• No severe diarrhea (greater than grade 3) that is not controllable with medication or that requires total parenteral nutrition

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• More than 4 weeks since prior interferon alfa
• No concurrent immunotherapy

Chemotherapy:

• More than 4 weeks since prior melphalan or other alkylating agents
• No prior anthracycline exposure greater than 120 mg/m^2
• Recovered from prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• More than 4 weeks since prior high-dose dexamethasone

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No concurrent investigational ancillary therapy