RATIONALE: 4'-Iodo-4'-deoxydoxorubicin may improve organ dysfunction and ease symptoms caused by primary systemic amyloidosis.

PURPOSE: Phase II trial to study the effectiveness of 4'-iodo-4'-deoxydoxorubicin in treating patients who have primary systemic amyloidosis.

Condition	Treatment or Intervention	Phase
primary systemic amyloidosis	Drug: '-iodo-4'-deoxydoxorubicin	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the clinical efficacy of 4'-iodo-4'-deoxydoxorubicin in producing palliation of symptoms and/or improvement of organ dysfunction caused by organ infiltration by amyloid in patients with primary systemic amyloidosis.

II. Assess the safety profile, with emphasis on cardiac safety, of this drug in these patients.

III. Evaluate the time to progression of amyloidosis-associated clinical symptoms and/or organ dysfunction, duration of response, and survival of these patients on this regimen.

PROTOCOL OUTLINE: Patients receive 4'-iodo-4'-deoxydoxorubicin IV over 1 hour once a week for 4 weeks. Courses are repeated every 12 weeks. Treatment continues for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histochemically proven primary systemic amyloidosis (AL); No presence of non-AL amyloidosis; No amyloid-specific syndrome (e.g., skin purpura or carpal tunnel syndrome) as only evidence of disease; No vascular amyloid only in a bone marrow biopsy specimen or in a plasmacytoma
• Must have symptomatic organ involvement with amyloid (e.g., liver, mild cardiac, renal, or soft tissue involvement, or grade 1 or 2 peripheral neuropathy)
• Demonstrable M-protein in the serum/urine OR Clonal population of plasma cells in the bone marrow OR Immunohistochemical stain with anti-light chain antisera of amyloid fibrils
• No clinically overt multiple myeloma (i.e., monoclonal BMPC greater than 20% and at least one of the following: bone lesions, anemia, or hypercalcemia)

--Prior/Concurrent Therapy--

• Biologic therapy: At least 6 weeks since prior interferon alfa
• Chemotherapy: No prior anthracyclines greater than 120 mg/m2; At least 6 weeks since prior melphalan or other alkylating agents
• Endocrine therapy: At least 6 weeks since prior high dose dexamethasone
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-3
• Life expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Total bilirubin less 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); ALT or AST no greater than 3 times ULN
• Renal: Creatinine clearance greater than 40 mL/min
• Cardiovascular: Echocardiographic ejection fraction greater than 50%; At least 3 years since prior enzyme documented myocardial infarction; Interventricular septal thickness no greater than 20 mm; No New York Heart Association class III or IV heart failure; No grade 2 or 3 A-V block; No chronic atrial fibrillation; No sustained (greater than 30 seconds) ventricular tachycardia or frequent episodes (greater than 20 in 24 hours) of nonsustained ventricular tachycardia or ventricular pairs, detected by 24-hour ambulatory electrocardiographic monitoring
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception; HIV positive allowed; No uncontrolled infection; No severe diarrhea not controllable with medication or that requires total parenteral nutrition; No other concurrent active malignancy except nonmelanoma skin cancer or cervical cancer

Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Italy
      University of Pavia, Pavia,  27100,  Italy

Study chairs or principal investigators

Morie Abraham Gertz,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000067016; MAYO-988003; NCI-T98-0003
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003853
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08