Forodesine in the Treatment of Cutaneous T-Cell Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00501735
First received: July 12, 2007
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

This is a Phase II, non-randomized, open-label, single-arm trial that will be conducted at up to 50 sites in North America, Europe and Australia. This study is designed to assess objective response (OR) [complete response (CR) or partial response (PR)] in subjects with cutaneous manifestations of CTCL with a requirement for maintenance of such objective response for at least 28 days in subjects with stage IIB, III, and IVA CTCL. Additionally, this study will evaluate the safety and tolerability of CTCL subjects Stages IB, IIA, IIB, III, or IVA treated with oral forodesine.


Condition Intervention Phase
Cutaneous T-cell Lymphoma (CTCL),
Drug: Forodesine 200 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single Agent Phase II Study of Forodesine (BCX1777) in the Treatment of Cutaneous T-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by BioCryst Pharmaceuticals:

Primary Outcome Measures:
  • The primary objective of this study is to determine the objective response rate to treatment with oral forodesine in subjects with cutaneous manifestations of CTCL subjects, stages IIB, III, and IVA. [ Time Frame: Duration of Study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability [ Time Frame: Duration of Study ] [ Designated as safety issue: Yes ]
  • Time to and duration of objective response in cutaneous manifestations [ Time Frame: Duration of Study ] [ Designated as safety issue: No ]
  • Time to loss of objective response [ Time Frame: Duration of Study ] [ Designated as safety issue: No ]
  • Objective response rate, time to and duration of extracutaneous manifestations [ Time Frame: Duration of Study ] [ Designated as safety issue: No ]
  • Health related quality of life [ Time Frame: Duration of Study ] [ Designated as safety issue: No ]

Enrollment: 144
Study Start Date: July 2007
Study Completion Date: December 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Forodesine 200 mg
    2 x 100mg tablets once daily
  Eligibility

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

Inclusion Criteria:

  • Males or non-pregnant females aged ≥18 years;
  • Histologically confirmed diagnosis of CTCL, including mycosis fungoides and/or Sezary syndrome, documentation of diagnosis by histologic examination should be available;
  • Subjects with CTCL stages IB, IIA, IIB, III, or IVA at the screening visit (i.e. stage refers to stage at study entry) and who have persistent, progressive, or recurrent disease during or following treatment with at least three forms of systemic therapy, one of which must have been oral bexarotene, unless treatment with oral bexarotene was not tolerated or was medically contraindicated;
  • Anticipated life expectancy greater than 6 months;
  • Performance status of 0, 1, or 2 by Eastern Cooperative Oncology Group (ECOG) criteria;
  • Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of study treatment;
  • Females of childbearing potential and sexually active males, if indicated, must be willing and able to use method(s) of contraception that are adequate to prevent or minimize the risk of pregnancy for the duration of the study;
  • Written informed consent to participate in the study.

Exclusion Criteria:

  • Proven or suspected extracutaneous visceral CTCL involvement (M1) (CTCL stage IVB) (note: presence of lymphadenopathy is permitted);
  • Previous treatment with Forodesine;
  • ECOG performance status >2;
  • Concomitant use of any anti-cancer therapy or immune modifier;
  • Concomitant use of any investigational agent or device;
  • Concurrent treatment with any other anti-CTCL therapy, or radiation therapy [topical corticosteroids (classes 1 and 2 prohibited) or low dose oral corticosteroids (≤10 mg/day prednisone or equivalent) will not be excluded, but if used, must be a stable dose and schedule during the four weeks immediately prior to study entry];
  • Use of previous therapies for CTCL within the timeframes specified below:

    1. Phototherapy in the previous 30 days;
    2. Electron beam therapy, photopheresis, systemic anticancer therapy, interferon therapy, or other investigational therapy in the previous 30 days;
    3. Oral retinoid (including bexarotene) in the previous 30 days
    4. Alemtuzumab (Campath) or other monoclonal antibody within the previous 30 days
    5. Vorinostat or other HDAC inhibitor within previous 30 days
    6. Any investigational therapy within the previous 30 days;
  • ALT or AST >3 times ULN or alkaline phosphatase >2 times ULN;
  • Calculated creatinine clearance ≤50 mL/min or serum creatinine ≥1.8 mg/dL;
  • Serum potassium <3.3 mg/dL or >5.5 mg/dL;
  • Evidence of clinically significant (uncontrolled) hypo- or hyperthyroidism;
  • Recent (in past 6 months) medically significant cardiac event (i.e., myocardial infarction, cardiac surgery);
  • Presence of congestive heart failure (NYHA class IV) or angina (NYHA class IV) or presence of a medically significant dysrhythmia;
  • Presence of any of the following ECG findings:

    1. Congenital long QT syndrome;
    2. QTc interval >480 msec (Bazett's correction);
  • Presence of uncontrolled hypertension manifested by systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥90 mmHg;
  • Hemoglobin <9.0 gm/dL (intermittent red blood cell transfusions permitted);
  • Absolute neutrophil count <1500 cells/mm3;
  • Platelet count <75,000/mm3;
  • Requirement for neutrophil or platelet growth factor therapy or administration of such therapy in the previous 30 days;
  • CD4 count <200/mm3;
  • Documented current active infection with HIV, Hepatitis B, Hepatitis C, and/or CMV;
  • Presence of uncontrolled bacterial or viral infection (subject may be receiving chronic antimicrobial therapy); or,
  • History of culture-documented bacteremia in the previous 2 weeks;
  • Recent (i.e., in past 2 weeks) change in doses or regimens of medications used for any chronic non-oncologic condition for reasons of worsening of the chronic illness (change in doses of chronic medications associated with improvement in a chronic illness are not exclusionary);
  • Presence of any acute or chronic non-oncologic disease which, in the opinion of the investigator, is medically uncontrolled;
  • Coexistent second malignancy or history of prior malignancy within previous 5 years [excluding basal cell or squamous cell carcinoma of skin and cervical neoplasia (carcinoma-in-situ) that has been treated curatively]. Surgically resected nonmelanomatous skin cancer (non-CTCL) with no evidence of recurrence in previous 6 months is permitted; and,
  • Any significant medical or psychiatric condition that, in the opinion of the investigator, might prevent the subject from complying with all required study procedures.
  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: NCT00501735

  Show 41 Study Locations
Sponsors and Collaborators
BioCryst Pharmaceuticals
Investigators
Principal Investigator: Nashat Gabrail, MD Gabrail Cancer Center
Principal Investigator: Madeleine Duvic, MD M.D. Anderson Cancer Center - Dermatology
Principal Investigator: Youn Kim, MD Stanford University
Principal Investigator: Andres Forero-Torres, M.D. University of Alabama at Birmingham, Comprehensive Cancer Ctr.
Principal Investigator: Alan B Fleischer, Jr., MD Wake Forest School of Medicine
Principal Investigator: Gary S. Wood, MD University of Wisconsin-Madison, Dept of Dermatology
Principal Investigator: Andre Goy, MD Hackensack Universeity Medical Ctr
Principal Investigator: Larisa Geskin, MD Hillman Cancer Ctr., University of Pittsburgh
Principal Investigator: Nancy Bartlett, MD Washington University School of Medicine
Principal Investigator: Francine Foss, MD Yale University
Principal Investigator: Miles Prince, MD Cabrini Hospital
Principal Investigator: Elise Olsen, MD Duke University
Principal Investigator: Sareeta S Parker, MD Emory University
Principal Investigator: Neil J Korman, MD, PhD University Hospitals Case Medical Ctr., Dept. of Dermatology
Principal Investigator: Francesco Turturro, MD LSU Health Sciences Ctr., Feist-Weiller Cancer Center
Principal Investigator: Andrei R Shustov, MD Seattle Cancer Care Alliance
  More Information

No publications provided

Responsible Party: BioCryst Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00501735     History of Changes
Other Study ID Numbers: BCX1777-203
Study First Received: July 12, 2007
Last Updated: January 18, 2012
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Finland: Finnish Medicines Agency
Switzerland: Swissmedic
Italy: Ethics Committee
Austria: Agency for Health and Food Safety

Keywords provided by BioCryst Pharmaceuticals:
T-Cell
Lymphoma
Forodesine
Mycosis Fungoides

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on July 28, 2014