This phase II trial is studying how well vorinostat works in treating patients with relapsed or refractory indolent non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To evaluate the anti-tumor activity of SAHA (vorinostat) as assessed by the objective response rate, time to progression and survival in subjects with advanced lymphoma. II. To assess the toxicity profile of SAHA in this patient population. III. To perform correlative laboratory investigations to confirm modulation of chromatin acetylation as the biologic target and attempt to gain insight into the downstream molecular mechanisms involved in the induction of apoptosis mediated by SAHA. OUTLINE: Patients receive vorinostat orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Correlative studies
Given PO
City of Hope Comprehensive Cancer Center
Duarte, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Response Rate
Radiological assessment by CT and/or PET scan after every three cycles (every 3 months). Response assessed by the standard Cheson criteria (Cheson et al, J Clin Oncol 17:1244, 1999). Complete Remission (CR) - (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative (b) Variably FDG-avid or PET negative; regression to normal size on CT; Partial Remission (PR) - 50% or greater decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes (a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT. Response Rate = CR + PR.
Time frame: Up to 3 years
Number of Participants With Adverse Events
Grades 3 \& 4 adverse events definitely, probably or possibly related to treatment, graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
Time frame: Up to 3 years
Change in Histone Acetylation by Immunohistochemistry (IHC)
Histone acetylation by IHC will be scored as -, +, ++, or +++, reflecting both the intensity of staining as well as the number of cells stained. Analysis will be descriptive, with the goal of describing baseline distributions and estimating the frequency and degree of changes from baseline.
Time frame: Baseline to up to day 14
Change in Histone Acetylation by Western Blot (WB)
Histone acetylation by WB will be recorded as the ratio of acetylated histone (measured by photodensitometry) divided by the total histone (H3 or H4), in order to control for the amount of protein loaded. Analysis will be descriptive, with the goal of describing baseline distributions and estimating the frequency and degree of changes from baseline.
Time frame: Baseline to up to day 14
2-Year Overall Survival
Estimated using the product-limit method of Kaplan and Meier.
Time frame: Until Death from any cause, up to 2 years
2-Year Progression Free-Survival
Estimated using the product-limit method of Kaplan and Meier. Progression defined as any new lesion or increase by greater than 50% of previously involved sites from nadir.
Time frame: Until death or progression, up to 2 years
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