Iododoxorubicin in Treating Patients With Primary Systemic Amyloidosis

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00030381
First received: February 14, 2002
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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 Intervention Phase
Primary Systemic Amyloidosis
Drug: 4'-iodo-4'-deoxydoxorubicin
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of 4'-IODO-4'-Deoxydoxorubicin in Primary Amyloidosis (AL)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • Laboratory correlates [ Time Frame: Up to 3 months post treatment ] [ Designated as safety issue: No ]
    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.


Enrollment: 22
Study Start Date: December 2001
Primary Completion Date: January 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00030381

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Angela Dispenzieri Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00030381     History of Changes
Other Study ID Numbers: NCI-2012-02443, MC0113, U01CA069912, CDR0000069160
Study First Received: February 14, 2002
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Doxorubicin
Esorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014