Phase I Trial of 4'-IODO-4'-Deoxydoxorubicin in Primary Amyloidosis (AL)
I. Determine the maximum tolerated dose of iododoxorubicin in patients with primary systemic
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
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.
United States: Food and Drug Administration
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