A Phase I Study of Arsenic Trioxide and Ascorbic Acid (ATO/AA) in Combination With Low Dose Velcade-Thalidomide-Dexamethasone (VTD) in Relapsed/Refractory Multiple Myeloma (MM)
- Determine the dose-limiting toxicity of arsenic trioxide when given in combination with
ascorbic acid, bortezomib, thalidomide, and dexamethasone, particularly in terms of
sensory neuropathy, in patients with relapsed or refractory multiple myeloma or plasma
- Determine the overall response rate, complete response rate, and response duration in
patients treated with the maximum tolerated dose of this regimen.
- Determine whether the addition of arsenic trioxide and ascorbic acid to the treatment
regimen (beginning in course 2) increases NFKB inhibition in these patients during
courses 2 and 3 compared to course 1.
OUTLINE: This is a multicenter, dose-escalation study of arsenic trioxide.
- Induction therapy: Patients receive bortezomib IV over 3-5 seconds and dexamethasone IV
or orally on days 1, 4, 8, and 11 and oral thalidomide once daily on days 1-21 (course
1). For course 2 and all subsequent courses, patients receive arsenic trioxide IV over
1-2 hours, ascorbic acid IV over 15 minutes, bortezomib IV over 3-5 seconds, and
dexamethasone IV or orally on days 1, 4, 8, and 11 and thalidomide once daily on days
1-21. Courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity. Patients who achieve a plateau in response proceed to
- Maintenance therapy: Patients receive oral dexamethasone every other day and oral
thalidomide once daily 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 determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine if arsenic trioxide and ascorbic acid at doses up to 0.25 mg/mg/dose can be given in combination with reduced-dose dexamethasone, bortezomib and thalidomide without dose limiting toxicity, especially sensory neuropathies.
Days 1, 4, 8 & 11 of each 21 day cycle
Jeffrey A. Zonder, MD
Barbara Ann Karmanos Cancer Institute
United States: Federal Government
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|