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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00383565
First received: September 29, 2006
Last updated: May 2, 2014
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Mantle Cell Lymphoma
Drug: romidepsin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment [ Time Frame: 24 weeks (6 courses of 4 week cycles) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Median Progression Free-survival (PFS) [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Time to disease progression is defined as the time from registration to documentation of disease progression.

  • Median Overall Survival [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    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.


Enrollment: 9
Study Start Date: September 2006
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive FR901228 IV over 4 hours on days 1, 8, and 15.
Drug: romidepsin
Given IV
Other Names:
  • FK228
  • FR901228
  • Istodax

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00383565

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Jorge Romaguera M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00383565     History of Changes
Other Study ID Numbers: NCI-2009-00240, NCI-2009-00240, 2005-0579, CDR0000486326, 2005-0579, 7869, P30CA016672, N01CM62202
Study First Received: September 29, 2006
Results First Received: July 19, 2012
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Romidepsin
Histone Deacetylase Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014