A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma
I. Determine the minimally effective pharmacological dose (MEPD) of single-agent decitabine
in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.
II. Determine the maximum tolerated dose of valproic acid when administered with the MEPD of
decitabine in these patients.
III. Determine the MEPD of valproic acid when administered with decitabine in these
IV. Determine the toxic effects of decitabine alone and in combination with valproic acid in
I. Determine the response rate in patients treated with these drugs. II. Determine the
pharmacokinetics of these drugs in these patients.
OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 treatment stages.
STAGE 1: Patients receive decitabine IV over 1 hour on days 1-5 or 1-10. Treatment repeats
every 28 days for up to 12 courses in the absence of disease progression or unacceptable
STAGE 2: Patients receive decitabine as in stage 1 and valproic acid orally (PO) thrice
daily (TID) on days 5-21. Treatment repeats every 28 days for up to 12 courses in the
absence of disease progression or unacceptable toxicity.
For both stages, patients who achieve an objective response (complete response [CR],
unconfirmed CR, or partial response) may discontinue study treatment and undergo stem cell
transplantation, if eligible.
PROJECTED ACCRUAL: Approximately 18-42 patients (18 for stage 1 and 24 for stage 2) will be
accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
MEPD of single agent decitabine defined as the dose where an 80% decrease in DNMT1 protein level and a 100% increase in re-expression of the methylated target genes are noted in 5 of 6 patients, with DLT in less than or equal to 1 patient
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|