Phase I/II Trial of Arsenic Trioxide (As2O3) With Ascorbic Acid in the Treatment of Relapsed/Refractory Multiple Myeloma
- Determine the maximum tolerated dose of arsenic trioxide when administered with
ascorbic acid in patients with recurrent or refractory multiple myeloma.
- Determine the therapeutic efficacy of this treatment combination in these patients.
- Determine the expression of MDR and Bcl-xL genes and the intracellular levels of GSH in
these patients before and after this treatment regimen and assess whether these
measures have prognostic value.
OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.
- Phase I: Patients receive arsenic trioxide IV over 1-4 hours and ascorbic acid IV over
5-10 minutes on days 1-5 weekly for 5 weeks. Treatment continues every 7 weeks for up
to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum
tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which 2 of
3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive the MTD of arsenic trioxide with ascorbic acid as outlined
Patients are followed monthly for up to 5 years.
PROJECTED ACCRUAL: A total of 31-43 patients (6-18 for phase I and 16-25 for phase II) will
be accrued for this study within 2.5 years.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Disease response as measured by M protein quantitation and the percentage of plasma cell infiltration in bone marrow biopsies after every course
Kelvin Lee, MD
University of Miami Sylvester Comprehensive Cancer Center
United States: Federal Government
|University of Miami Sylvester Comprehensive Cancer Center||Miami, Florida 33136|
|Baptist-South Miami Regional Cancer Program||Miami, Florida 33176|
|Cedars Medical Center||Miami, Florida 33136|
|Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center||Miami Beach, Florida 33140|