Trial Information

A Phase I/II Trial of Vorinostat (SAHA) (NSC-701852) in Combination With Rituximab-CHOP in Patients With Newly Diagnosed Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL)

OBJECTIVES:

I. To find a safe dose of vorinostat to be used in combination with R-CHOP in patients with
newly diagnosed stage II-IV diffuse large B-cell lymphoma. (Phase I) II. To estimate the
2-year progression-free survival (PFS) rate in patients treated with this regimen. (Phase
II) III. To estimate the response rate (complete and partial) and 2-year overall survival
rate. (Phase II) IV. To evaluate the toxicity of this regimen in these patients. (Phase II)
V. To assess whether pre-treatment acetylation status of histones, expression of MHC Class
II genes, and/or percentage of CD8+ tumor infiltrating lymphocytes correlate with PFS.
(Phase II) VI. To explore whether treatment with vorinostat-R-CHOP increases histone
acetylation, alters expression of MHC class II proteins, or alters percentage of T-cell
subsets (CD8+, CD4+, FOXP3+) or infiltrating macrophages. (Phase II) VII. To explore whether
histone acetylation status of tumor tissues correlates with MHC class II expression of
peripheral blood B cells and lymphocyte subsets. (Phase II) VIII. To explore whether the
change in systemic levels of immune cytokines with vorinostat-R-CHOP correlates with
lymphoma symptoms, response, PFS, or overall survival. (Phase II)

OUTLINE: This is a multicenter, phase I dose escalation study of vorinostat followed by a
phase II study.

Patients receive vorinostat orally (PO) once daily on days 1-5 or 1-9 (according to dose
level), rituximab intravenously (IV), cyclophosphamide IV over 30-60 minutes, doxorubicin
hydrochloride IV, and vincristine sulfate IV on day 3. Patients also receive prednisone PO
once daily on days 3-7. Treatment repeats every 21 days for 8 courses in the absence of
disease progression or unacceptable toxicity.

Paraffin block, core needle biopsy, and whole blood samples may be collected at baseline and
during the first course of treatment for further analysis.

After completion of study treatment, patients are followed every 6 months for 2 years, and
then annually for 3 years.