A Japanese Phase 1/2 Study to Assess the Efficacy, Safety and Pharmacokinetics of Romidepsin in Patients With Peripheral T-cell Lymphoma (PTCL)

Inclusion Criteria

Patients must fulfill all of the following criteria to be eligible for study participation and have:

• Histologically confirmed Peripheral T cell Lymphoma (PTCL) Not Otherwise Specified (NOS), Angioimmunoblastic T-cell Lymphoma, enteropathy- type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous T-cell lymphoma (excludes mycosis fungoides or Sezary syndrome) , hepatosplenic T-cell lymphoma, Anaplastic Large cell lymphoma (ALCL) [anaplastic lymphoma kinase-1 (ALK-1) negative], patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after Autologous Stem-Cell Transplantation, Transformed mycosis fungoides (MF), or Sézary syndrome (SS);
• Age ≥20 years;
• Written informed consent;
• Progressive Disease following at least one systemic therapy or refractory to at least one prior systemic therapy;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• Sufficient functions of bone marrow or other organs as evidenced by
• Hemoglobin ≥8.0 g/dL (The value after the 7th day of transfusion)
• Absolute neutrophil count (ANC) ≥1.0×10^9/L (The value after the 7th day of G-CSF)
• Platelet counts ≥100 x 10^9/L, or, if bone marrow infiltration is recognized, ≥75 ×10^9/L
• Total bilirubin (Total-Bil) ≤2 x upper limit of normal (ULN) (≤3.0 x ULN in the presence of demonstrable liver metastasis)
• Aspartate Aminotransferase (AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT) ≤2 x Upper Limit Normal (ULN) (≤3.0 x ULN in the presence of demonstrable liver metastasis)
• Alanine Aminotransferase (ALT)/Serum Glutamic-Oxaloacetic Transaminase (SGOT) ≤2 x ULN (≤3.0 x ULN in the presence of demonstrable liver metastasis)
• Serum creatinine ≤ 2 x ULN
• Serum potassium ≥ lower limit of normal (LLN) and magnesium
• Patients for whom at least 1 measurable lesion is confirmed in the lesion assessment before enrollment; and
• Negative urine or serum pregnancy test on females of childbearing potential.

Exclusion Criteria: Confirmation should be made before enrollment, and the subjects corresponding to the criteria should not be enrolled.

• Subjects in whom central nervous lymphoma is recognized during the screening period (If brain metastasis is suspected clinically, CT should be performed.)
• Subjects undergoing chemotherapy or immunotherapy for the purpose of treatment of the target disease within 22 days before C1D1 (including C1D1) (using antibody drugs only within 3 months before C1D1)
• Subjects receiving local application of steroids within 15 days before C1D1 (including C1D1) Use of steroids for the purpose other than that of treatment of the target disease should be allowed (Only CTCL subjects)
• Subjects receiving systemic application of steroids within 22 days before C1D1 (including C1D1) (It is acceptable to continue the use of the steroid for the purpose of treatment of the target disease,which administered in doses ≤ 10mg/day prednisolone or equivalent dose of other glucocorticoid. However increase of steroid dose cannot be allowed during the study period)
• Subjects undergoing radiation therapy, PUVA therapy or TSEB for the purpose of treatment of the target disease within 22 days before C1D1 (including C1D1)
• Subjects using other investigational products within 22 days before C1D1 (including C1D1) (using antibody drugs only within 3 months before C1D1)
• Subjects undergoing blood transfusion and using G-CSF within 8 days before C1D1 (including C1D1)
• Subjects with the following abnormalities in the cardiac function
• Congenital QT prolongation syndrome
• QTc interval >480 msec
• Myocardial infarction within 6 months before C1D1. Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may occur
• Significant ECG abnormalities including atrio-ventric