E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cutaneous T-cell lymphoma (CTCL) (Peripheral T-cell lymphoma unspecified NOS) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 5.0 |
E.1.2 | Level | CTEP |
E.1.2 | Classification code | 10034624 |
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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 |
To confirm the efficacy of FK228, depsipeptide, as reported in the Phase I and early Phase II studies, in patients with CTCL who are no longer controlled on skin-directed therapy and who have had at least one prior systemic therapy. The rate of objective disease control, as determined by Objective Primary Disease Response Evaluation Criteria (OPDREC) will be used as the primary endpoint to assess efficacy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate duration and durability of objective disease response, and time to objective disease prgression. To evaluate the safety of FK228 in terms of adverse events, clinical laboratory data, physical examinations, ECG findings, rate of neutropenic fever and sepsis, blood transfusions, and treatment compliance. To evaluate the pharmacokinetics of FK228 in a cohort of patients with CTCL. To evaluate disease status with molecular markers in PBMCs and potentially tumours, including acetylation status, apoptosis markers, STAT, AKT and caspases. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Males or non-pregnant females aged >=18 years. Histologically confirmed diagnosis of CTCL, including Mycosis fungoides / Sézary’s syndrome. Patients with CTCL stages IIa, IIb, III and IVa Patients with CTCL stage Ib who have relapsed following previous therapy and where, in the investigator’s opinion, the potential benefit of treatment with FK228 outweighs the possible risks.
Patients who have failed standard skin-directed therapy and have had only one course of systemic therapy, such as interferon, which they have also failed. Anticipated life expectancy greater than six months. Written informed consent to participate in the study. |
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E.4 | Principal exclusion criteria |
• ECOG Performance Status >1 • Patients who have not received at least 1 course of prior systemic therapy for CTCL. • Visceral involvement i.e. Stage 4b disease (lymphadenopathy is allowed). • Patients with known cardiac abnormalities such as:- Congenital long QT syndrome QTc interval > 480 milliseconds Any cardiac arrhythmia requiring anti-arrhythmic medication. • Patients who have had a myocardial infarction within 12 months of study entry. • Patients who have a history of coronary artery disease (CAD) e.g. angina Canadian class II to IV . In any patient in whom there is doubt, the patient should have a stress imaging study and exercise ECG and, if abnormal, angiography to define whether or not CAD is present. • Patients with an ECG recorded at screening showing evidence of cardiac ischaemia (ST depression of 2 mm). If in any doubt, the patient should have a stress imaging study and exercise ECG and, if abnormal, angiography to define whether or not CAD is present. • Patients with congestive heart failure that meets New York Heart Association class II to IV definitions and/or ejection fraction <40% by multiple gated acquisition (MUGA) scan or <50% by echocardiogram and/or magnetic resonance imaging (MRI) • Patients with a history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest, unless currently addressed with an automatic implantable cardioverter defibrillator (AICD). • Patients with hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above). • Patients with uncontrolled hypertension, i.e. >160/95 mmHg. • Concomitant use of any anti-cancer therapy. (For study eligibility, a one month washout period is required before treatment with depsipeptide is started for patients who have received radiotherapy or psoralen plus ultraviolet A (PUVA) therapy.) • Concomitant use of warfarin. • Concomitant use of any investigational agent. • Use of any investigational agent within 4 weeks before treatment with depsipeptide is started. • Concomitant use of drugs which may cause a prolongation of the QTc interval. (For study eligibility, a washout period of at least 5 half-lives must elapse before treatment with depsipeptide is started. ) • Patients with a potassium level of <3.5 mmol/L and a magnesium level of <0.8 mmol/L. • Clinically significant active infection. • Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. • Inadequate bone marrow or other organ function, as evidenced by: o unsupported haemoglobin <9.0 g/dL (transfusions and/or erythropoietin are permitted); o absolute neutrophil count (ANC) </=1.5 x 109/L; o platelet count <100 x 109/L; o total bilirubin >1.25 x upper limit of normal (ULN) for institution; o aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) >2.0 x ULN, serum creatinine >2 x ULN for age and sex. • Coexistent second malignancy or history of prior malignancy within previous 5 years (excluding basal or squamous cell carcinoma of the skin or cervical epithelial neoplasm [CIN1, carcinoma in situ] that has been treated curatively). • Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures. • Patients who are pregnant or breast-feeding. All women of child bearing potential must use an effective method of contraception (either an intrauterine device or a double barrier method using condoms or a diaphragm plus spermicide) during the study and for at least 1 month after receiving the last dose of depsipeptide. Male patients must use a barrier method of contraception (condoms) during the treatment period and for at least 1 month thereafter. Hormonal methods of contraception such as the contraceptive pill or patch (particularly those containing ethinyl-estradiol) should be avoided due to a potential drug interaction. • Use of topical steroids in the previous 2 weeks or systemic steroids in the previous 4 weeks before treatment with depsipeptide is started. • Having previously given consent to participate in this study. • Concomitant use of CYP3A4 inhibitors
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E.5 End points |
E.5.1 | Primary end point(s) |
The rate of objective disease control defined as confirmed complete response (CR), complete clinical response (CCR), partial response (PR), or stable disease (SD, for SD with a duration of at least 3 months) as determined by the Objective Primary Disease Response Evaluation Criteria (OPDREC). |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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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Last visit of the last patient |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |