Clinical trial NCT00501735: Forodesine in the Treatment of Cutaneous T-Cell Lymphoma
Official title: Single Agent Phase II Study of Forodesine (BCX1777) in the Treatment of Cutaneous T-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cutaneous T-cell Lymphoma (CTCL),
Keywords: T-Cell
Lymphoma
Forodesine
Mycosis Fungoides
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2007-07-16
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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.
timeFrame: Duration of Study
Secondary outcomes:
measure: Safety and tolerability
timeFrame: Duration of Study
measure: Time to and duration of objective response in cutaneous manifestations
timeFrame: Duration of Study
measure: Time to loss of objective response
timeFrame: Duration of Study
measure: Objective response rate, time to and duration of extracutaneous manifestations
timeFrame: Duration of Study
measure: Health related quality of life
timeFrame: Duration of Study
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham, Comprehensive Cancer Ctr
state: Alabama
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Shreveport
country: United States
facility: LSU Health Sciences Center, Feist-Weiller Cancer Center
state: Louisiana
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Ctr
state: New Jersey
city: Syracuse
country: United States
facility: Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sceinces, Dept. of Dermatology
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center, Dept. of Dermatology
state: Ohio
city: Philadelphia
country: United States
facility: Hospital at the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Ctr., University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: M.D. Anderson Cancer Center - Dermatology
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Madison, Dept of Dermatology
state: Wisconsin
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
city: Wien
country: Austria
facility: Wien
city: Helsinki
country: Finland
facility: Helsinki
city: Clermont-Ferrand
country: France
facility: Hopital Hotel-Dieu
city: Creteil
country: France
facility: Creteil
city: Montpellier
country: France
facility: Montpellier
city: Pessac
country: France
facility: Pessac
city: Reims CEDEX
country: France
facility: CHU Robert Debre
city: Toulouse
country: France
facility: Toulouse
city: Berlin
country: Germany
facility: Campus Charité Mitte
city: Jena
country: Germany
facility: Universitatsklinikum Jena
city: Kiel
country: Germany
facility: Universitat Kiel
city: Mannheim
country: Germany
facility: Klinik fur Dermatologie, Venerologie und Allergologie
city: Bologna
country: Italy
facility: Bologna
city: Firenze
country: Italy
facility: Firenze
city: Milan
country: Italy
facility: Milan
city: Rome
country: Italy
facility: Rome
city: Torino
country: Italy
facility: Torino
city: Madrid
country: Spain
facility: Madrid
city: Zurich
country: Switzerland
facility: Zurich
city: London
country: United Kingdom
facility: London
city: Manchester
country: United Kingdom
facility: Manchester
Study officials:
affiliation: Gabrail Cancer Center
name: Nashat Gabrail, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center - Dermatology
name: Madeleine Duvic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Youn Kim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham, Comprehensive Cancer Ctr.
name: Andres Forero-Torres, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: Alan B Fleischer, Jr., MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin-Madison, Dept of Dermatology
name: Gary S. Wood, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hackensack Universeity Medical Ctr
name: Andre Goy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hillman Cancer Ctr., University of Pittsburgh
name: Larisa Geskin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Nancy Bartlett, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Francine Foss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cabrini Hospital
name: Miles Prince, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Elise Olsen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Sareeta S Parker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospitals Case Medical Ctr., Dept. of Dermatology
name: Neil J Korman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: LSU Health Sciences Ctr., Feist-Weiller Cancer Center
name: Francesco Turturro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Cancer Care Alliance
name: Andrei R Shustov, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.