A Phase I/II Study of Vorinostat Plus Rituximab, Ifosphamide, Carboplatin, and Etoposide for Patients With Relapsed or Refractory Lymphoid Malignancies or Untreated T- or Mantle Cell Lymphoma
I. To determine maximally tolerated dose of vorinostat that can be combined with RICE
chemotherapy in patients with relapsed lymphoid malignancies.
II. To determine the safety and toxicity of the above regimen. III. To gain a preliminary
assessment of the efficacy of the above regimen. IV. To determine the ability to proceed to
peripheral blood stem cell collection following the above regimens (the impact of above
regimen on stem cell reserve).
V. To describe vorinostat concentration attained at or near the MTD. VI. To evaluate the
change of histone acetylation patterns and pro-apoptotic proteins of primary target (tumor)
and non-target peripheral blood mononuclear cells (PBMC) cells following high-dose HDAC
VII. To describe the gene expression profile changes of tumor and non-tumor cells following
high-dose HDAC inhibition.
OUTLINE: This is a phase I/II dose-escalation study of vorinostat.
Patients receive vorinostat orally (PO) once daily (QD) on days 1-5, ifosfamide IV
continuously over 24 hours and carboplatin IV over 1 hour on day 4, and etoposide IV over 1
hour on days 3-5. Patients who are CD20+ also receive rituximab IV once on day 3, 4, or 5.
Treatment repeats every 21 days for 2 courses in the absence of disease progression or
After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months for 4 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of vorinostat
28 days post last dose of study drug
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Institutional Review Board
|Puget Sound Oncology Consortium||Seattle, Washington 98109|