FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

A Phase II Study of Depsipeptide, a Histone Deacetylase Inhibitor, in Relapsed or Refractory Mantle Cell or Diffuse Large Cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00383565
• Other study ID #: NCI-2009-00240
• Secondary ID: NCI-2009-0024020
• Status: Terminated
• Phase: Phase 2
• First received: September 29, 2006
• Last updated: May 2, 2014
• Start date: September 2006
• Est. completion date: April 2011

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

FR901228 may stop the growth of cancer cells by blocking some of the enzymes needed for cell to grow and by blocking blood flow to the cancer. This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Description:

OBJECTIVES:

I. Determine the response rate (complete and partial) to FR901228 in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma.

II. Evaluate the safety and feasibility of FR901228, in terms of the incidence of toxicity and maximum grade observed and courses delayed or dose reductions, in these patients.

III. Determine 2-year progression-free and overall survival.

OUTLINE: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15.

Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: April 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma of 1 of the following subtypes:

• Mantle cell lymphoma

• Diffuse large cell lymphoma

• (Ineligible for or unwilling to undergo stem cell transplantation)

• Relapsed or refractory disease:

• Any number of prior therapies allowed for relapsed disease, including peripheral blood stem cell or bone marrow transplantation

• No more than 2 prior regimens, excluding monotherapy with monoclonal antibody or radiotherapy, for refractory disease

• Measurable disease, defined as >= 1 lesion >= 1.5 cm in the longest diameter

• No transformed lymphoma, defined as the transformation of a low-grade lymphoma, including follicular lymphoma or small lymphocytic lymphoma, to a high-grade lymphoma (e.g., diffuse large cell lymphoma)

• ECOG performance status 0-2

• Absolute neutrophil count >= 1,000/mm^3 OR >= 500/mm^3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly

• Platelet count >= 75,000/mm^3 OR >= 50,000/mm^3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly

• Bilirubin normal

• Alkaline phosphatase =< 2 times upper limit of normal (ULN)

• AST =< 2 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No significant cardiac disease, including New York Heart Association class III-IV congestive heart failure

• No history of serious ventricular arrhythmia

• QTc < 500 msec

• No evidence of cardiac hypertrophy on ECG

• No known HIV positivity

• No other uncontrolled serious medical condition or active infection (e.g., chronic obstructive pulmonary disease, diabetes)

• Recovered from prior therapy

• No prior doxorubicin hydrochloride >= 450 mg/m^2 or mitoxantrone >= 112 mg/m^2 (Patients who received both mitoxantrone and doxorubicin hydrochloride should have a "doxorubicin equivalent dose" < 450 mg/m^2

• No prior therapy with a histone deacetylase inhibitor

• No concurrent dexamethasone or prednisone except for refractory nausea/vomiting

• No concurrent drugs associated with QTc prolongation (e.g., dolasetron mesylate)

• Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is receiving potassium chloride supplementation (No supplementation needed if switched to a potassium-conserving diuretic)

• No CNS lymphoma

• Creatinine normal

• Cardiac function >= 50% by MUGA

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Recurrent Adult Diffuse Large Cell Lymphoma
• Recurrent Mantle Cell Lymphoma

Intervention

Drug:
• romidepsin
Given IV

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment	International Working Group response for non- Hodgkin's lymphoma: Complete Response (CR) - disappearance all detectable clinical/radiographic evidence of disease and disappearance of all disease-related symptoms (present before therapy) and normalization of those biochemical abnormalities; Partial Response (PR) - =50% decrease in sum products of greatest diameters (SPD) of 6 largest dominant nodes or nodal masses, selected by clearly measurable in at least two perpendicular dimensions, from disparate regions of body and no decrease in size of other nodes, liver, or spleen.	24 weeks (6 courses of 4 week cycles)	No
Secondary	Median Progression Free-survival (PFS)	Time to disease progression is defined as the time from registration to documentation of disease progression.	2 Years	No
Secondary	Median Overall Survival	Survival time is defined as the time from registration to death due to any cause, measured in months. The distribution of survival time estimated using the method of Kaplan-Meier.	5 Years	No