A Phase II Study of Single Agent Depsipeptide (NSC 630176) Followed by a Phase I Study of Rituximab/Fludarabine Combination With an Escalating Dose of Depsipeptide in Relapsed or Refractory Low Grade B Cell Lymphomas
I. For phase 2: is to assess the clinical efficacy (complete and partial response rates) of
single agent depsipeptide.
II. For phase 1: is to assess the feasibility of adding Depsipeptide to a regimen of
Rituximab and Fludarabine and to establish the MTD of Depsipeptide in this combination.
I. To correlate disease response (clinical outcome) with the changes in histone acetylation
II. Study the expression of death receptors of DR4 and DR5 after treatment with
III. Assessment of minimal residual disease by immune histochemistry.
OUTLINE: This is a multicenter, phase II study of single-agent FR901228 followed by a phase
I, dose-escalation study of FR901228.
PHASE II: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15. Treatment repeats
every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients who achieve a complete or partial remission receive 2 additional courses (for a
total of 6 courses). Patients with stable disease after 4 courses or progressive disease at
any time after 2 courses proceed to the phase I portion of the study.
PHASE I: Patients receive rituximab IV over approximately 4-8 hours on day 1; fludarabine IV
over 10-30 minutes on days 2-4; and FR901228 IV over 4 hours on days 2, 9, and 16. Treatment
repeats every 28 days for up to 6 courses in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of FR901228 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity.
Patients are followed for up to 3 years from study entry.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective response rate (Phase II)
Exact confidence interval of the response rate will be calculated.
Up to 3 years
University of Maryland Greenebaum Cancer Center
United States: Food and Drug Administration
|University of Maryland Greenebaum Cancer Center||Baltimore, Maryland 21201|