Iododoxorubicin in Treating Patients With Primary Systemic Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00030381
Recruitment Status : Terminated (Administratively complete.)
First Posted : September 17, 2003
Last Update Posted : January 16, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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

Condition or disease Intervention/treatment Phase
Primary Systemic Amyloidosis Drug: 4'-iodo-4'-deoxydoxorubicin Other: pharmacological study Phase 1

Detailed Description:


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


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of 4'-IODO-4'-Deoxydoxorubicin in Primary Amyloidosis (AL)
Study Start Date : December 2001
Actual Primary Completion Date : January 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Amyloidosis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: 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.
Drug: 4'-iodo-4'-deoxydoxorubicin
Given IV
Other Names:
  • IDOX
  • iododoxorubicin
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Primary Outcome Measures :
  1. MTD of IDOX defined as the highest safely-tolerated dose where =< 1 patient experiences DLT with the next higher dose having at least 2 patients who experience DLT [ Time Frame: 12 weeks ]
    The number and severity of toxicity incidents will indicate the level of tolerance of IDOX in the treatment of primary amyloidosis. Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization via CTC standard toxicity grading.

Secondary Outcome Measures :
  1. Laboratory correlates [ Time Frame: Up to 3 months post treatment ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and non-parametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing of these data will be carried out via standard Shapiro and Wilk (25) testing.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00030381

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Angela Dispenzieri Mayo Clinic

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00030381     History of Changes
Other Study ID Numbers: NCI-2012-02443
U01CA069912 ( U.S. NIH Grant/Contract )
CDR0000069160 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: September 17, 2003    Key Record Dates
Last Update Posted: January 16, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Proteostasis Deficiencies
Metabolic Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action