Forodesine in the Treatment of Cutaneous T-Cell Lymphoma

NCT ID: NCT00501735

Last Updated: 2012-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2011-12-31

Brief Summary

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.

Conditions

Cutaneous T-cell Lymphoma (CTCL),

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Forodesine 200 mg

2 x 100mg tablets once daily

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioCryst Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nashat Gabrail, MD

Role: PRINCIPAL_INVESTIGATOR

Gabrail Cancer Center

Madeleine Duvic, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center - Dermatology

Youn Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Andres Forero-Torres, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham, Comprehensive Cancer Ctr.

Alan B Fleischer, Jr., MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Gary S. Wood, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin-Madison, Dept of Dermatology

Andre Goy, MD

Role: PRINCIPAL_INVESTIGATOR

Hackensack Universeity Medical Ctr

Larisa Geskin, MD

Role: PRINCIPAL_INVESTIGATOR

Hillman Cancer Ctr., University of Pittsburgh

Nancy Bartlett, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Francine Foss, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Miles Prince, MD

Role: PRINCIPAL_INVESTIGATOR

Cabrini Hospital

Elise Olsen, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Sareeta S Parker, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Neil J Korman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Case Medical Ctr., Dept. of Dermatology

Francesco Turturro, MD

Role: PRINCIPAL_INVESTIGATOR

LSU Health Sciences Ctr., Feist-Weiller Cancer Center

Andrei R Shustov, MD

Role: PRINCIPAL_INVESTIGATOR

Seattle Cancer Care Alliance

Locations

University of Alabama at Birmingham, Comprehensive Cancer Ctr

Birmingham, Alabama, United States

Stanford University Medical Center

Stanford, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

LSU Health Sciences Center, Feist-Weiller Cancer Center

Shreveport, Louisiana, United States

Boston Medical Center

Boston, Massachusetts, United States

Washington University School of Medicine

St Louis, Missouri, United States

Hackensack University Medical Ctr

Hackensack, New Jersey, United States

Upstate Medical University

Syracuse, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sceinces, Dept. of Dermatology

Winston-Salem, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

University Hospitals Case Medical Center, Dept. of Dermatology

Cleveland, Ohio, United States

Hospital at the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Hillman Cancer Ctr., University of Pittsburgh

Pittsburgh, Pennsylvania, United States

M.D. Anderson Cancer Center - Dermatology

Houston, Texas, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

University of Wisconsin-Madison, Dept of Dermatology

Madison, Wisconsin, United States

Cabrini Hospital

Malvern, Victoria, Australia

Wien

Vienna, , Austria

Helsinki

Helsinki, , Finland

Hopital Hotel-Dieu

Clermont-Ferrand, , France

Creteil

Créteil, , France

Montpellier

Montpellier, , France

Pessac

Pessac, , France

CHU Robert Debre

Reims, , France

Toulouse

Toulouse, , France

Campus Charité Mitte

Berlin, , Germany

Universitatsklinikum Jena

Jena, , Germany

Universitat Kiel

Kiel, , Germany

Klinik fur Dermatologie, Venerologie und Allergologie

Mannheim, , Germany

Bologna

Bologna, , Italy

Firenze

Florence, , Italy

Milan

Milan, , Italy

Rome

Rome, , Italy

Torino

Torino, , Italy

Madrid

Madrid, , Spain

Zurich

Zurich, , Switzerland

London

London, , United Kingdom

Manchester

Manchester, , United Kingdom

Countries

United States; Australia; Austria; Finland; France; Germany; Italy; Spain; Switzerland; United Kingdom

References

Dummer R, Duvic M, Scarisbrick J, Olsen EA, Rozati S, Eggmann N, Goldinger SM, Hutchinson K, Geskin L, Illidge TM, Giuliano E, Elder J, Kim YH. Final results of a multicenter phase II study of the purine nucleoside phosphorylase (PNP) inhibitor forodesine in patients with advanced cutaneous T-cell lymphomas (CTCL) (Mycosis fungoides and Sezary syndrome). Ann Oncol. 2014 Sep;25(9):1807-1812. doi: 10.1093/annonc/mdu231. Epub 2014 Jun 19.

Reference Type: DERIVED

PMID: 24948692 (View on PubMed)

Other Identifiers

BCX1777-203

Identifier Type: -

Identifier Source: org_study_id