Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
Nodal Marginal Zone Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Indolent Non-Hodgkin's Lymphoma|
- Response rate (complete remission + partial remission) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Exact binomial 95% confidence intervals will be provided.
- Change in histone acetylation by immunohistochemistry (IHC) and Western Blot (WB) [ Time Frame: Baseline to up to day 14 ] [ Designated as safety issue: No ]Histone acetylation by IHC will be scored as -, +, ++, or +++, reflecting both the intensity of staining as well as the number of cells stained; and histone acetylation by WB will recorded as the ratio of acetylated histone (measured by photodensitometry) divided by the total histone (H3 or H4), in order control for the amount of protein loaded. Analysis will be primarily descriptive, with the goal of describing baseline distributions and estimating the frequency and degree of changes from baseline.
- Incidence of adverse events as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]Recorded by type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.
- Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Estimated using the product-limit method of Kaplan and Meier.
- Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]Estimated using the product-limit method of Kaplan and Meier.
|Study Start Date:||September 2005|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (vorinostat)
Patients receive vorinostat PO BID on days 1-14. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Vorinostat
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00253630
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|City of Hope South Pasadena|
|South Pasadena, California, United States, 91030|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Leslie Popplewell||Beckman Research Institute|