Cutaneous T-cell Lymphoma (CTCL), Clinical Trial
Official title:
Single Agent Phase II Study of Forodesine (BCX1777) in the Treatment of Cutaneous T-Cell Lymphoma
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.
| Status | Completed |
| Enrollment | 144 |
| Est. completion date | December 2011 |
| Est. primary completion date | July 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | Cabrini Hospital | Malvern | Victoria |
| Austria | Wien | Wien | |
| Finland | Helsinki | Helsinki | |
| France | Hopital Hotel-Dieu | Clermont-Ferrand | |
| France | Creteil | Creteil | |
| France | Montpellier | Montpellier | |
| France | Pessac | Pessac | |
| France | CHU Robert Debre | Reims CEDEX | |
| France | Toulouse | Toulouse | |
| Germany | Campus Charité Mitte | Berlin | |
| Germany | Universitatsklinikum Jena | Jena | |
| Germany | Universitat Kiel | Kiel | |
| Germany | Klinik fur Dermatologie, Venerologie und Allergologie | Mannheim | |
| Italy | Bologna | Bologna | |
| Italy | Firenze | Firenze | |
| Italy | Milan | Milan | |
| Italy | Rome | Rome | |
| Italy | Torino | Torino | |
| Spain | Madrid | Madrid | |
| Switzerland | Zurich | Zurich | |
| United Kingdom | London | London | |
| United Kingdom | Manchester | Manchester | |
| United States | Emory University | Atlanta | Georgia |
| United States | University of Alabama at Birmingham, Comprehensive Cancer Ctr | Birmingham | Alabama |
| United States | Boston Medical Center | Boston | Massachusetts |
| United States | Gabrail Cancer Center | Canton | Ohio |
| United States | University Hospitals Case Medical Center, Dept. of Dermatology | Cleveland | Ohio |
| United States | Duke University Medical Center | Durham | North Carolina |
| United States | Hackensack University Medical Ctr | Hackensack | New Jersey |
| United States | M.D. Anderson Cancer Center - Dermatology | Houston | Texas |
| United States | University of Wisconsin-Madison, Dept of Dermatology | Madison | Wisconsin |
| United States | Yale Cancer Center | New Haven | Connecticut |
| United States | Hospital at the University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Hillman Cancer Ctr., University of Pittsburgh | Pittsburgh | Pennsylvania |
| United States | Seattle Cancer Care Alliance | Seattle | Washington |
| United States | LSU Health Sciences Center, Feist-Weiller Cancer Center | Shreveport | Louisiana |
| United States | Washington University School of Medicine | St. Louis | Missouri |
| United States | Stanford University Medical Center | Stanford | California |
| United States | Upstate Medical University | Syracuse | New York |
| United States | Moffitt Cancer Center | Tampa | Florida |
| United States | Wake Forest University Health Sceinces, Dept. of Dermatology | Winston-Salem | North Carolina |
| Lead Sponsor | Collaborator |
|---|---|
| BioCryst Pharmaceuticals |
United States, Australia, Austria, Finland, France, Germany, Italy, Spain, Switzerland, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Duration of Study | No | |
| Secondary | Safety and tolerability | Duration of Study | Yes | |
| Secondary | Time to and duration of objective response in cutaneous manifestations | Duration of Study | No | |
| Secondary | Time to loss of objective response | Duration of Study | No | |
| Secondary | Objective response rate, time to and duration of extracutaneous manifestations | Duration of Study | No | |
| Secondary | Health related quality of life | Duration of Study | No |