A Phase I Study of SAHA in Combination With Bortezomib in Relapsed and Refractory Multiple Myeloma
I. Determine the maximum tolerated dose (MTD) of vorinostat (SAHA) when given together with
bortezomib in patients with relapsed or refractory multiple myeloma (MM).
II. Determine the toxicity of this regimen in these patients.
I. Determine whether giving SAHA together with bortezomib inhibits histone deacetylation in
normal cells (buccal mucosal cells and/or peripheral blood monocytes) as well as in MM
II. Evaluate the effect of dexamethasone when given together with SAHA and bortezomib.
III. Explore molecular mechanisms involved in apoptosis in MM mediated by SAHA and
IV. Correlate change of histone acetylation with clinical outcome in patients treated with
OUTLINE: This is a multicenter, dose escalation study of vorinostat (SAHA).
Patients receive bortezomib IV on days 1, 4, 8, and 11 followed by oral SAHA twice daily on
days 4-11. Beginning in course 3, some patients may receive low-dose oral dexamethasone on
days 4-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA 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. An additional cohort of 10 patients receive
treatment at the MTD.
Patients undergo blood collection and tumor biopsies periodically during study for
pharmacologic and biomarker correlative studies.
After completion of study treatment, patients are followed at least once a month.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of SAHA in combination with bortezomib determined by dose-limiting toxicities
University of Maryland Greenebaum Cancer Center
United States: Food and Drug Administration
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|