E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Cutaneous T-cell Lymphomas (CTCL) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028483 |
E.1.2 | Term | Mycosis fungoides |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to determine the objective repsonse rate to treatment with oral forodesine in subjects with cutaneous manifestations of CTCL, stages IIb, III and IVa |
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E.2.2 | Secondary objectives of the trial |
1. Assess the safety and tolerability of daily administration of oral forodesine in this population 2. Determine the time to objective repsonse in subjects with CTCL having cutaneous manifestations of the disease 3. Determine the duration of objective repsonse in subjects with CTCL haing cutaneous manifestations of the disease 4. Determine the loss of objective response 5. Determine the objective response rate of extracutaneous manifestations of CTCL (lymph node enlargment, Sezary cells in peripheral blood) 6. Determine the time to objective response and duration of objective response of extracutaneous manifestations of CTCL in subjects who have extracutaneous manifestations of disease 7 Determine subjects assessment of treatment related changes in health related quality of life (HRQoL). |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Males and non-pregnant femails aged ≥ 18 years 2. Histologically confirmed diagnbosis 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 treament with at least three forms of systemic therpay one of which must have been bexarotene, unless treatment with oral bexarotene was not tolerated or was medically contraindicated 4. Anitipated life expectancy > 6 months 5. Performance status of 0,1 or 2 by ECOG 6. Females of child bearing potential must have a negative serum prenancy test within 14 days prior to intiation 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 mimimize the risk of pregnancy for the duration of the study 8. Written informed consent to participate in the study |
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E.4 | Principal exclusion criteria |
CTCL related 1. Proven or suspected extracutaneous visceral CTCL involvement (M1) (CTCL stage IVb)prescence of lymphadenopathy is permitted 2. Previous treatment with forodesine 3. ECOG performance status >2 4. Concomitant use of any anti-cancer therpay or immune modifer 5 Concomitant use of any investigational agent or device 6. Concomitant treatment with any other anti-CTCL therapy or radiation therapy. Topical corticosteriods (except clases 1 and 2 which are prohibited) or low dose oral corticosteriods (≤10 mg/day prednisone or equivalent) will not be excluded, but if used must be a stable dose and schedle during the four weeks immediately prior to the study entry 7. Use of previous therapies for CTCL withi the previous 30 days: a)Phototherapy b. electron beam therapy, photophoresis, systemic anticancer therpay, interferon therapy, or other investigational therapy c. oral retinoid (including bexarotene) d. Alemtuzumab (Campath) or other monoclonal antibody e. Vorinostat or other HDAC inhibitor f. any investigational therapy Hepatic/Renal/ Metabolic EXcl Criteria 8. ALT or AST > 3 times ULN or alkaline phosphatase >2 times ULN 9. Calculated creatinine clearance ≤50ml/min or serum creatine ≥1.8 mg/dl 10 Serum potassium <3.3mg/dl or >5.5 mg/dl 11. Evidence of clinically significant (uncontrolled) hypo or hyperthyroidism CArdiovascular criteria 12. REcent(in the past 6 months) medically significant cardiac event 13. Prescence of congestive heart failure (NYHA IV) or angina (NYHA class IV) or prescence of a medically significant dysrhythmia 14. Prescence of the following ECG findings a. Congenital long QT syndrome; b. QTc interval >480 msec (Bazetts correction); 14. Presence of uncontrolled hypertension manifested by systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥90 mmHg; Hematologic Exclusion Criteria 15. Hemoglobin <9.0 gm/dL (intermittent red blood cell transfusions permitted); 16. Absolute neutrophil count <1500 cells/mm3; 17. Platelet count <75,000/mm3; 18. Requirement for neutrophil or platelet growth factor therapy or administration of such therapy in the previous 30 days; 19. CD4 count <200/mm3; Infection-Related Exclusion Criteria 20. Documented current active infection with HIV, Hepatitis B, Hepatitis C, and/or CMV; 21. Presence of uncontrolled bacterial or viral infection (subject may be receiving chronic antimicrobial therapy); or, 22. History of culture-documented bacteremia in the previous 2 weeks. General Exclusion Criteria 23. 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); 24. Presence of any acute or chronic non-oncologic disease which, in the opinion of the investigator, is medically uncontrolled; 25. 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-insitu) that has been treated curatively]. Surgically resected nonmelanomatous skin cancer (non-CTCL) with no evidence of recurrence in previous 6 months is permitted; and, 26. Any significant medical or psychiatric condition that, in the opinion of the investigator, might prevent the subject from complying with all required study procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endoint 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 IIB, III or IVa. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |