Ensayo de agente único en fase II sobre la forodesina (BCX1777) en el tratamiento del linfoma cutáneo de células T - forodesine in CTCL

• Register: EUCTR
• Last refreshed on: 28 August 2014
• Main ID: EUCTR2007-002093-60-ES
• Date of registration: 06/02/2008
• Prospective Registration: Yes
• Primary sponsor: BioCryst Pharmaceuticals, Inc.
• Public title: Ensayo de agente único en fase II sobre la forodesina (BCX1777) en el tratamiento del linfoma cutáneo de células T - forodesine in CTCL
• Scientific title: Ensayo de agente único en fase II sobre la forodesina (BCX1777) en el tratamiento del linfoma cutáneo de células T - forodesine in CTCL
• Date of first enrolment: 17/04/2008
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002093-60
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Austria, Denmark, France, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Males or non-pregnant females aged =18 years;
2. Histologically confirmed diagnosis of CTCL, including mycosis fungoides and/or sezary syndrome;
3. Subjects with CTCL stages IB, IIA, IIB, III or IVA 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 bexarotene, unless treatment with oral bexarotene was not tolerated or was medically contraindicated;
4. Anticipated life expectancy > 6 months;
5. Performance status of 0, 1, or 2 by ECOG;
6. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of study treatment ;
7. Females of child bearing 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; and,
8. Written informed consent to participate in the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
CTCL-related Exclusion Criteria

1. Proven or suspected extracutaneous visceral CTCL involvement (M1) (CTCL stage IVB) (note: presence of lymphadenopathy is permitted);
2. Previous treatment with forodesine;
3. ECOG performance status >2;
4. Concomitant use of any anti-cancer therapy or immune modifier;
5. Concomitant use of any investigational agent or device;
6. Concurrent treatment with any other anti-CTCL therapy, or radiation therapy. Topical corticosteroids (except classes 1 and 2 which are 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;
7. Use of previous therapies for CTCL within the timeframes specified below:
a. Phototherapy in the previous 30 days;
b. Electron beam therapy, photopheresis, systemic anticancer therapy, interferon therapy, or other investigational therapy in the previous 30 days;
c. Oral retinoid (including bexarotene) in the previous 30 days;
d. Alemtuzumab (Campath) or other monoclonal antibody within the previous 30 days
e. Vorinostat or other HDAC inhibitor within previous 30 days
f. Any investigational therapy within the previous 30 days;

Hepatic/Renal/Metaboli Exclusion Criteria

8. ALT or AST >3 times ULN or alkaline phosphatase >2 times ULN;
9. Calculated creatine clearance =50mL/min or serum creatine =1.8mg/dL;
10. Serum potassium <3.3mg/dL or >5.5mg/dL;
11. Evidence of clinically significant (uncontrolled) hypo- or hyperthyroidism;

Cardiovascular Exclusion Criteria

12. Recent (in past 6 months) medically significant cardiac event (i.e., myocardial infarction, cardiac surgery);
13. Presence of congestive heart failure (NYHA class IV) or angina (NYHA class IV) or presence of a medically significant dysrhythmia;
14. Presence of any of the following ECG findings:
a. Congenital long QT syndrome;
b. QTc interval >480 msec (Bazett’s correction);
15. Presence of uncontrolled hypertension manifested by systolic blood pressure =160mmHg and or diastolic blood pressure =90mmHg;

Hematologic Exclusion Criteria

16. Hemoglobin <9.0gm/dL (intermittent red blood cell transfusions permitted);
17. Absolute neutrophil count <1500cells/mm^3;
18. Platelet count <75,000/mm^3;
19. Requirement for neutrophil or platelet growth factor therapy or administration of such therapy in the previous 30 days;
20. CD4 count <200/mm^3

Infection-Related Exclusion Criteria

21. Documented current active infection with HIV, Hepatitis B, Hepatitis C and/or CMV;
22. Presence of uncontrolled bacterial or viral infection (subject may be receiving chronic antimicrobial therapy); or,
23. History of culture-documented bacteremia in the previous 2 weeks.

General Exclusion Criteria

24. 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);
25. Presence of any acute or chronic non-oncologic disease which, in the opinion of the investigator, is medically uncontrolled;
26. coexistent second malignancy or history of prior malignancy within 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)

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

linfoma cutáneo de células T (CTCLs)
MedDRA version: 9.1 Level: LLT Classification code 10028508 Term: Mycosis fungoides/Sezary syndrome

Intervention(s)

Product Name: Forodesine hydrochloride
Product Code: BCX1777
Pharmaceutical Form: Capsule*
Current Sponsor code: BCX1777
Other descriptive name: forodesine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: The secondary objectives are:

1. To assess the safety and tolerability of daily administration of oral forodesine in this population;
2. To determine the time to objective response in subjects with CTCL having cutaneous manifestations of the disease;
3. To determine the duration of objective response in subjects with CTCL having cutaneous manifestations of the disease;
4. To determine the loss of objective response;
5. To determine the objective response rate of extracutaneous manifestations of CTCL (lymph node enlargement, Sezary cells in peripheral blood).
6. To determine the time to objective response and duration of objective response of extracutaneous manifestations of CTCL in subjects who have extracutaneous manifestations of disease; and,
7. To determine subjects' assessments of treatment-related changes in health related quality of life (HRQoL).

Main Objective: The primary objective is to determine the objective response rate to treatment with oral forodesine in subjects with cutaneous manifestations of CTCL, stages IIb, III and IVa.

Primary end point(s): The primary end point is an assessment of objective response (OR) for each patient, defined as either complete cutaneous response (CR) or partial cutaneous response (PR), in subjects with CTCL Stages IIB, III, or IVA. Cutaneous response will be determined by use of a modified severity weighted assessment tool (mSWAT). Objective response will be defined as either no evidence of clinical disease or a marked improvement that is =50% decrease in mSWAT score compared to Baseline. Confirmation of objective response will be required by a second assessment after at least 28 days. At the time of confirmation of OR, CT scans (neck, chest, abdomen and pelvis) should be performed to confirm the absence of progression of any pre-existing lymph node disease involvement.
Cutaneous disease manifestations will be documented by serial standardised body photgraphy and skin assessment worksheets.

Secondary ID(s)

BCX1777-203

2007-002093-60-FR