Clinical trial NCT00106431 (phase 2, status: completed)
Conditions: cutaneous t-cell lymphoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: romidepsin (depsipeptide, fk228)
SMILES: C\C=C1/NC(=O)[C@H]2CSSCC\C=C\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C
Eligibility criteria:

        Inclusion Criteria: Patients had to fulfill all of the following criteria to be eligible
        for study participation:

          -  Males or non-pregnant females aged 18 or over.

          -  Histologically confirmed diagnosis of CTCL, including mycosis fungoides and Sézary
             syndrome.

          -  Patients with CTCL stages II-A, II-B, III, and IV-A only.

          -  Patients with CTCL stage IB who had relapsed following previous therapy and where, in
             the investigator's opinion, the potential benefit of treatment with romidepsin
             outweighed the possible risks.

          -  Patients who had failed standardized skin-directed therapy and had had at least one
             course of systemic therapy, such as interferon, Ontak®, chemotherapy or Targretin®,
             etc., which they were deemed to have failed.

          -  Anticipated life expectancy greater than six months.

          -  Written informed consent to participate in the study.

        Exclusion Criteria: Patients were ineligible for entry if any of the following criteria
        were met:

          -  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.