A Study of the Histone Deacetylase Inhibitor (HDACi) JNJ-26481585 in Patients With Previously Treated Stage Ib-IVa Cutaneous T-cell Lymphoma (CTCL)

• To determine overall cutaneous response (RR) rate, based on modified Severity Weighted Assessment Tool (mSWAT) criteria [ Time Frame: Up to two years ] [ Designated as safety issue: No ]
  The RR is defined as the proportion of evaluable subjects who achieve a CR (complete disappearance of all cutaneous disease) or PR (≥ 50% reduction in mSWAT score compared with baseline). mSWAT score : The skin tumor burden will be assessed according to mSWAT evaluation. The investigator will determine the percentage of total body surface area (TBSA) affected in 12 body regions, using the subject's palm and fingers representing 1% of TBSA.
  
  

• To determine overall global RR based on consensus global response score for mycosis fungoides (MF) / Sézary Syndrome (SS) (mSWAT + nodes/viscera + blood) [ Time Frame: Up to two years ] [ Designated as safety issue: No ]
  
• To evaluate adverse events [ Time Frame: Up to two years ] [ Designated as safety issue: Yes ]
  
• To determine the duration of response (DOR) [ Time Frame: First documentation of CR or PR until the date of first documentation of progressive disease (PD), or death ] [ Designated as safety issue: No ]
  The DOR for subjects achieving a CR or PR, defined as the date from the first documentation of CR or PR until the date of first documentation of progressive disease (PD), or death from any cause.
  
  
• To estimate progression-free survival (PFS) [ Time Frame: First dose of study drug and the date of disease progression or death ] [ Designated as safety issue: No ]
  The PFS, defined as the interval between the date of administration of the first dose of study drug and the date of disease progression or death from any cause, whichever occurs first
  
  
• To estimate 1-year overall survival (OS) rate [ Time Frame: First dose of study drug until death (up to 2 years) ] [ Designated as safety issue: No ]
  The Kaplan-Meier estimate of the proportion of subjects surviving at 1 year after the date of administration of the first dose of study drug
  
  
• To assess pharmacodynamic markers of JNJ-26481585 activity in tumor biopsies and surrogate tissues [ Designated as safety issue: No ]
  
• To explore biomarkers predictive of response to JNJ-26481585 [ Designated as safety issue: No ]
  
• To explore the population pharmacokinetics (PK) of JNJ-26481585 [ Designated as safety issue: No ]
  
• The European Organization for Research and Treatment (EORTC QLQ-C30) and the Pruritus Intensity Assessment Questionnaire scale scores [ Designated as safety issue: No ]
  The EORTC QLQ-C30 is the basic module with 30-items with appended other modules.The questionnaire includes nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, nausea and vomiting, pain); and a global health and quality of life scale. Other single item measures are also included (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact). The instrument contains 28 items using a Likert scale with 4 response options; 'Not at All,' 'A Little,' 'Quite a Bit,' to 'Very Much' (scored 1 to 4).
  
  

All patients entered in the study will receive treatment with JNJ-26481585. This study will have three phases: a Screening Phase (from signing of informed consent until immediately before dosing), a Treatment Phase (from the first dose of study drug until the End-of-Treatment Visit), and a Follow-up Phase (after the End-of-Treatment Visit until clinical cut-off). Clinical cut-off is defined as when the last patient in the study has been assessed with progressive disease or died, or 6 months after the last patient is randomly assigned to treatment, whichever occurs first. However, if any patients are still receiving study treatment at the time of clinical cut-off, these patients will enter a Long-term Extension Phase and continue to receive study treatment until a reason for discontinuation is met (ie, disease progression, toxicity, availability of other effective drugs that the patient may receive, or treating physician advice). The Long-term Extension Phase will continue for a maximum of 2 years beyond the clinical cut-off for primary analysis. Patients will be closely monitored for adverse events (AEs), laboratory abnormalities, and clinical response, according to the scheduled assessments. The patients will receive JNJ-26481585, 12 mg, orally on Days 1, 3, and 5 of each week in a 21-day treatment cycle. JNJ-26481585 is to be taken with approximately 200 mL of water once a day. Treatment will continue until disease progression or unacceptable toxicity occurs.