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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Terminated
CT.gov ID
NCT00383565
Collaborator
(none)
9
1
1
55
0.2

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OBJECTIVES:
  1. 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.

  2. 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.

  3. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
9 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 :
Sep 1, 2006
Actual Primary Completion Date :
Apr 1, 2011
Actual Study Completion Date :
Apr 1, 2011

Arms and Interventions

Arm Intervention/Treatment
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
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment [24 weeks (6 courses of 4 week cycles)]

      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

    1. Median Progression Free-survival (PFS) [2 Years]

      Time to disease progression is defined as the time from registration to documentation of disease progression.

    2. Median Overall Survival [5 Years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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/mm3 OR >= 500/mm3 if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly

    • Platelet count >= 75,000/mm3 OR >= 50,000/mm3 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/m2 or mitoxantrone >= 112 mg/m2 (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

    Locations

    Site City State Country Postal Code
    1 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Jorge Romaguera, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00383565
    Other Study ID Numbers:
    • NCI-2009-00240
    • NCI-2009-00240
    • 2005-0579
    • CDR0000486326
    • 2005-0579
    • 7869
    • P30CA016672
    • N01CM62202
    First Posted:
    Oct 3, 2006
    Last Update Posted:
    May 20, 2014
    Last Verified:
    Apr 1, 2013

    Study Results

    Participant Flow

    Recruitment Details Recruitment Period: September 20, 2006 to May 08, 2009. All recruitment done at UT MD Anderson Cancer Center.
    Pre-assignment Detail
    Arm/Group Title FR901228
    Arm/Group Description 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15
    Period Title: Overall Study
    STARTED 9
    COMPLETED 9
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title FR901228
    Arm/Group Description 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15
    Overall Participants 9
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    4
    44.4%
    >=65 years
    5
    55.6%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    66.8
    (12.6)
    Sex: Female, Male (Count of Participants)
    Female
    1
    11.1%
    Male
    8
    88.9%
    Region of Enrollment (participants) [Number]
    United States
    9
    100%

    Outcome Measures

    1. Primary Outcome
    Title Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment
    Description 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.
    Time Frame 24 weeks (6 courses of 4 week cycles)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title FR901228
    Arm/Group Description 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15
    Measure Participants 9
    Complete Response
    0
    0%
    Partial Response
    1
    11.1%
    2. Secondary Outcome
    Title Median Progression Free-survival (PFS)
    Description Time to disease progression is defined as the time from registration to documentation of disease progression.
    Time Frame 2 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title FR901228
    Arm/Group Description 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15
    Measure Participants 9
    Median (Full Range) [months]
    4
    3. Secondary Outcome
    Title Median Overall Survival
    Description 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.
    Time Frame 5 Years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title FR901228
    Arm/Group Description 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15
    Measure Participants 9
    Median (Full Range) [months]
    20

    Adverse Events

    Time Frame 3 years and 9 months
    Adverse Event Reporting Description
    Arm/Group Title FR901228
    Arm/Group Description 13 mg/m^2 FR901228 by vein (IV) over 4 hours on days 1, 8, and 15
    All Cause Mortality
    FR901228
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    FR901228
    Affected / at Risk (%) # Events
    Total 6/9 (66.7%)
    Cardiac disorders
    Cardiac Arrhythmia 1/9 (11.1%)
    Infectious Endocarditis 1/9 (11.1%)
    Eye disorders
    Diplopia 1/9 (11.1%)
    Gastrointestinal disorders
    Dysphagia 1/9 (11.1%)
    General disorders
    Death NOS 1/9 (11.1%)
    Non-neutropenic fever 1/9 (11.1%)
    Fatigue 1/9 (11.1%)
    Infections and infestations
    Neutropenia 1/9 (11.1%)
    Thrombocytopenia 2/9 (22.2%)
    Infection 1/9 (11.1%)
    Metabolism and nutrition disorders
    Glucose, serum-high 1/9 (11.1%)
    Increased Alkaline phosphatase 1/9 (11.1%)
    Vascular disorders
    DVT, Vascular access-related 1/9 (11.1%)
    Other (Not Including Serious) Adverse Events
    FR901228
    Affected / at Risk (%) # Events
    Total 9/9 (100%)
    Blood and lymphatic system disorders
    anemia 7/9 (77.8%)
    Cardiac disorders
    sinus tachycardia 1/9 (11.1%)
    Eye disorders
    blurry vision 2/9 (22.2%)
    Gastrointestinal disorders
    nausea 6/9 (66.7%)
    constipation 3/9 (33.3%)
    diarrhea 3/9 (33.3%)
    gastritis 1/9 (11.1%)
    hemorrhoids 1/9 (11.1%)
    mucositis oral 1/9 (11.1%)
    oral pain 1/9 (11.1%)
    periodontal disease 1/9 (11.1%)
    rectal pain 1/9 (11.1%)
    stomach pain 1/9 (11.1%)
    vomiting 3/9 (33.3%)
    taste alteration 1/9 (11.1%)
    General disorders
    fatigue 5/9 (55.6%)
    fever 2/9 (22.2%)
    edema limbs 2/9 (22.2%)
    Infections and infestations
    infection with normal Absolute neutrophil count (ANC) 7/9 (77.8%)
    sinusitis 1/9 (11.1%)
    Investigations
    weight loss 2/9 (22.2%)
    thrombocytopenia 8/9 (88.9%)
    alanine aminotransferase (ALT) 2/9 (22.2%)
    aspartate aminotransferase (AST) 3/9 (33.3%)
    alkaline phosphatase 3/9 (33.3%)
    creatinine 1/9 (11.1%)
    lymphopenia 6/9 (66.7%)
    leukopenia 3/9 (33.3%)
    neutropenia 2/9 (22.2%)
    Metabolism and nutrition disorders
    hyperglycemia 4/9 (44.4%)
    anorexia 2/9 (22.2%)
    hypocalcemia 2/9 (22.2%)
    hypoalbuminemia 4/9 (44.4%)
    hyperuricemia 1/9 (11.1%)
    hypoglycemia 1/9 (11.1%)
    hyperkalemia 4/9 (44.4%)
    hypomagnesemia 2/9 (22.2%)
    hyponatremia 2/9 (22.2%)
    hypophosphatemia 3/9 (33.3%)
    Musculoskeletal and connective tissue disorders
    myalgia 3/9 (33.3%)
    Nervous system disorders
    sensory neuropathy 2/9 (22.2%)
    dizziness 2/9 (22.2%)
    headache 1/9 (11.1%)
    Respiratory, thoracic and mediastinal disorders
    dyspnea 1/9 (11.1%)
    pneumonitis 1/9 (11.1%)
    cough 1/9 (11.1%)
    Skin and subcutaneous tissue disorders
    pruritus 1/9 (11.1%)
    Vascular disorders
    hypotension 1/9 (11.1%)
    thrombosis 1/9 (11.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Dr. Luis E. Fayad / Associate Professor
    Organization MD Anderson Cancer Center
    Phone 713-792-2860
    Email jmdennison@mdanderson.org
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00383565
    Other Study ID Numbers:
    • NCI-2009-00240
    • NCI-2009-00240
    • 2005-0579
    • CDR0000486326
    • 2005-0579
    • 7869
    • P30CA016672
    • N01CM62202
    First Posted:
    Oct 3, 2006
    Last Update Posted:
    May 20, 2014
    Last Verified:
    Apr 1, 2013