Iododoxorubicin in Treating Patients With Primary Systemic Amyloidosis

NCT ID: NCT00030381

Last Updated: 2013-01-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-12-31

Brief Summary

Iododoxorubicin may dissolve protein deposits and be an effective treatment for primary systemic amyloidosis. Phase I trial to determine the effectiveness of iododoxorubicin in treating patients who have primary systemic amyloidosis

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of iododoxorubicin in patients with primary systemic amyloidosis.

SECONDARY OBJECTIVES:

I. Determine the safety, especially cardiac safety, of this drug in these patients.

II. Determine the survival rate of patients treated with this drug. III. Determine, preliminarily, the clinical efficacy of this drug in these patients.

IV. 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.

Conditions

Primary Systemic Amyloidosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (iododoxorubicin)

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.

Group Type: EXPERIMENTAL

4'-iodo-4'-deoxydoxorubicin

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

4'-iodo-4'-deoxydoxorubicin

Given IV

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

IDOX; iododoxorubicin; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Histochemically confirmed amyloidosis by polarizing microscopy of greenbirefringent 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
• Performance status - ECOG 0-3 (3 allowed only if related to muscular infiltration by amyloid or peripheral neuropathy)
• Platelet count at least 100,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Total bilirubin no greater than 2.0 mg/dL
• 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
• Creatinine clearance at least 40 mL/min
• 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
• 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
• More than 4 weeks since prior interferon alfa
• No concurrent immunotherapy
• 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
• More than 4 weeks since prior high-dose dexamethasone
• No concurrent radiotherapy
• No concurrent investigational ancillary therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angela Dispenzieri

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

MC0113

Identifier Type: -

Identifier Source: secondary_id

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069160

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02443

Identifier Type: -

Identifier Source: org_study_id