| Exclusion Criteria: | 1) Known central nervous system (CNS) lymphoma [computed tomography (CT) or magnetic resonance imaging (MRI) scans are required only if brain metastasis is suspected clinically]
2) Chemotherapy or immunotherapy within 4 weeks of study entry (6 weeks if nitrosoureas given)
3) Initiation of corticosteroids during study (defined as 7 days prior to C1D1 until study drug discontinuation). Patients treated with a pulse of steroids must discontinue steriod use 7 days prior to C1D1 and have a repeat CT scan and disease assessment after discontinuation of corticosteroids and before starting romidepsin;
4) Concomitant use of any other anti-cancer therapy
5) Concomitant use of any investigational agent
6) Any known cardiac abnormalities such as: Congenital long QT syndrome; QTc interval >480 milliseconds (msec); Myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negatice cardiac risk assessment( treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate; Other significant ECG abnormalities including 2nd atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
7) Use of any investigational agent within 4 weeks of study entry
8) Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any patient in whom there is doubt, the patient should be referred to a cardiologist for evaluation; An ECG recorded at screening showing significant ST depression (ST depression of >/= 2 mm, measured from isoelectric line to the ST segment at a point 60 msec at the end of the QRS complex). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
9) Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction <40% by MUGA scan or <50% by echocardiogram and/or MRI; A known 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); Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above)
10) Uncontrolled hypertension, i.e., blood pressure (BP) of >/= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; Any cardiac arrhythmia requiring anti-arrhythmic medication;
11) Serum potassium < 3.8 mmol/L or serum magnesium < 0.85 mmol/L (magnesium converts to 2.0 mg/dl or 1.7mEq/L). Electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria;
12) Concomitant use of drugs that may cause a significant prolongation of the QTc;
13) Concomitant use of CYP3A4 significant or moderate inhibitors;
14) Concomitant use of therapeutic warfarin due to a potential drug interaction. Use of a low dose of warfarin or another anticoagulant to maintain patency of venous access port and cannulas is permitted.
15) Clinically significant active infection
16) Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
17) Previous extensive radiotherapy involving >/= 30% of bone marrow (e.g., whole pelvis, half spine), excluding patients who have had total body irradiation as part of a conditioning regimen for ASCT
18) Major surgery within 2 weeks of study entry (C1D1);
19) Previous allogeneic stem cell transplant
20) Inadequate bone marrow or other organ function as evidenced by: Hemoglobin < 9 g/dL (transfusions and/or erythropoietin are permitted); Absolute neutrophil count (ANC)</= 1.0 × 10^9 cells/L [patients with neutropenia (ANC 1–1.5) as a function of their disease may be supported with granulocyte-colony stimulating factor (G-CSF)]
21) Platelet count <100 × 10^9 cells/L or platelet count <75 × 10^9 cells/L if bone marrow disease involvement is documented; Total bilirubin >2.0 × upper limit of normal (ULN) or >3.0 × ULN in the presence of demonstrable liver metastases
22) Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) >2.0 × ULN or >3.0 × ULN in the presence of demonstrable liver metastases; or
23) Serum creatinine >2.0 × ULN;
24) Patients who are pregnant or breast-feeding;
25) Coexistent second malignancy or history of prior solid organ malignancy within previous 3 years (excluding basal or squamous cell carcinoma of the skin, and in situ carcinoma of the cervix (CIN 3) that has been treated curatively);
26) Any prior history of a hematologic malignancy (other than T-cell lymphoma);
27) Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures; or
28) Prior exposure to romidepsin (other HDAC inhibitors are allowed). |