Phase I Trial of Arsenic Trioxide in Combination With Pamidronate Disodium
I. To describe the toxicities of the combination of arsenic trioxide in combination with
pamidronate disodium at four dose levels.
II. To assess the pharmacokinetics of pamidronate disodium when given in combination with
III. Utilizing 2-color immunofluorescence (IF) to determine if the treatment with
combination of arsenic trioxide and pamidronate disodium affects the phosphorylation of
epidermal growth factor receptor (EGFR) IV. In patients with multiple myeloma utilizing
western blot to evaluate the pre- and post-treatment levels of protein tyrosine phosphatase
1B in lysates of multiple myeloma cells.
V. To obtain preliminary data for response to this regimen in this patient population.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive pamidronate IV and over 2 hours on days 1 and 15 and arsenic trioxide IV
over 2 hours on days 1-5 and 15-19. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of pamidronate and arsenic trioxide until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of 6 patients experience dose limiting toxicity.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: Approximately 12-24 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as the highest dose tested in which greater than 33% of patients experienced dose limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course. Tabular and graphical summaries will be used to explore the relationship of type and grade of toxicity to dose, course, and pharmacokinetics.
Beckman Research Institute
United States: Food and Drug Administration
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