A Single Agent Phase II Study of Romidepsin (Depsipeptide, FK228) in the Treatment of Cutaneous T-cell Lymphoma (CTCL)

Exclusion Criteria

• •ECOG Performance Status \>1.
• •Patients who had not received at least 1 course of prior systemic therapy for CTCL.
• •Visceral involvement i.e. Stage 4B disease (lymphadenopathy was allowed).
• •Patients with known cardiac abnormalities such as:
• •* Congenital long QT syndrome
• •* QTc (Corrected QT interval on ECG) interval \>480 milliseconds
• •* Any cardiac arrhythmia requiring anti-arrhythmic medication.
• •Patients who had had a myocardial infarction within 12 months of study entry.
• •Patients who had a history of coronary artery disease (CAD) e.g. angina Canadian class II to IV. In any patient in whom there was doubt, the patient should have had a stress imaging study and exercise electrocardiogram (ECG) and, if abnormal, angiography to define whether or not CAD was 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 had 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 met 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.
• •Concomitant use of warfarin (due to a drug interaction).
• •Concomitant use of any investigational agent.
• •Use of any investigational agent within 4 weeks of study entry.
• •Concomitant use of drugs which may cause a prolongation of the QTc interval.
• •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:
• •* unsupported haemoglobin \<9.0 g/dL (transfusions and/or erythropoietin were permitted);
• •* absolute neutrophil count (ANC) \<=1.5 x 10\^9/L;
• •* platelet count \<100 x 10\^9/L;
• •* total bilirubin \>1.25 x upper limit of normal (ULN) for institution,
• •* aspartate transaminase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/ glutamic pyruvic transaminase (ALT/SGPT) \>2.0 x ULN, serum creatinine \>2.0 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 had been treated curatively).
• •Any significant medical or psychiatric condition that might have prevented the patient from complying with all study procedures.
• •Patients who were pregnant or breast-feeding. All women of child bearing potential were to 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 one month after receiving the last dose of romidepsin. Male patients were to 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) were to 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.
• •Having previously given consent to participate in this study.
• •Concomitant use of CYP3A4 inhibitors.