NCT00079443

FR901228 Alone or Combined With Rituximab and Fludarabine in Treating Patients With Relapsed or Refractory Low-Grade B-Cell Non-Hodgkin's Lymphoma

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial is studying the best dose of FR901228 when given together with rituximab and fludarabine and to see how well FR901228 works alone in treating patients with relapsed or refractory low-grade B-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as FR901228 and fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Rituximab may increase the effectiveness of chemotherapy drugs by making cancer cells more sensitive to the drugs.

Detailed description

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: I. To correlate disease response (clinical outcome) with the changes in histone acetylation assays. II. Study the expression of death receptors of DR4 and DR5 after treatment with depsipeptide. 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 unacceptable toxicity. 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.

Conditions

• Recurrent Grade 1 Follicular Lymphoma
• Recurrent Grade 2 Follicular Lymphoma
• Recurrent Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	romidepsin	Given IV
BIOLOGICAL	rituximab	Given IV
DRUG	fludarabine phosphate	Given IV
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2004-01-01
• Primary completion: 2005-09-01
• First posted: 2004-03-10
• Last updated: 2013-07-01

Locations

1 site across 1 country: United States