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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00077194

Collaborator

(none)

Enrollment

Locations

Arm

8.8

Patients Per Site

Study Details

Study Description

Brief Summary

This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as FR901228, work in different ways to stop tumor cells from dividing so they stop growing or die.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: romidepsin	Phase 2

Detailed Description

OBJECTIVES:

Determine the response rate (complete and partial) in patients with relapsed or refractory Burkitt's, mantle cell or diffuse large cell non-Hodgkin's lymphoma treated with FR901228 (depsipeptide).
Determine the safety and feasibility of this drug, in terms of incidence and maximum grade of toxicity and courses delayed or doses reduced, in these patients.
Determine the 2-year progression-free survival and overall survival of patients treated with this drug.
Correlate tumor expression of BCL-2, BCL-6, BAX, and RAS with response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive FR901228 (depsipeptide) 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.

Patients are followed every 3 months until disease progression and then every 6 months until 5 years from study registration.

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2004

Actual Primary Completion Date :

Dec 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive FR901228 (depsipeptide) 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.	Drug: romidepsin

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive FR901228 (depsipeptide) 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.

Drug: romidepsin

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma of 1 of the following cellular types:
Diffuse large cell
Mantle cell
Burkitt's
Relapsed or refractory disease
No more than 2 prior regimen for patients with refractory disease
Any number of prior therapies (including peripheral blood stem cell or bone marrow transplantation) allowed for patients with relapsed disease provided there was an objective response to the most recent therapy
Measurable disease
At least 1 lesion ≥ 1.5 cm in diameter
No transformed lymphoma
No CNS lymphoma
Ineligible for, refused, or relapsed after stem cell transplantation

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Hematopoietic

Absolute neutrophil count ≥ 1,000/mm^{3 (500/mm}3 in patients with extensive bone marrow involvement [> 50%] or hypersplenism with palpable splenomegaly)
Platelet count ≥ 75,000/mm^{3 (50,000/mm}3 in patients with extensive bone marrow involvement or hypersplenism with palpable splenomegaly)

Hepatic

Bilirubin ≤ upper limit of normal (ULN)
Alkaline phosphatase ≤ 2 times ULN
AST ≤ 2 times ULN

Renal

Creatinine ≤ ULN

Cardiovascular

QTc < 500 msec by ECG
Cardiac function ≥ 50% by MUGA
No prior serious ventricular arrhythmia
No New York Heart Association class III or IV congestive heart failure
No significant cardiac hypertrophy by ECG
No other significant cardiac disease

Pulmonary

No chronic obstructive pulmonary disease

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No active infection
No diabetes
No other uncontrolled serious medical condition

PRIOR CONCURRENT THERAPY:

Chemotherapy

Prior cumulative doxorubicin dose < 450 mg/m^2
Prior cumulative mitoxantrone dose < 112 mg/m^2
Prior doxorubicin equivalent dose < 450 mg/m^2 (for patients who have previously received both doxorubicin and mitoxantrone)

Other

Recovered from all prior therapy
No prior histone deacetylase inhibitor therapy
No concurrent medication associated with QTc prolongation, such as dolasetron
Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is on concurrent potassium chloride supplementation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Howard University Cancer Center at Howard University Hospital	Washington	District of Columbia	United States	20060
2	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231
3	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
4	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-5256