Trial Information

Summary: A Single-Agent Phase II Trial of Romidepsin (Depsipeptide) in the Treatment of Progressive or Relapsed Peripheral T-cell Lymphoma (PTCL)

The purpose of this study is to evaluate the activity of romidepsin in patients with progressive or relapsed peripheral T-cell lymphoma (PTCL) who have already been treated with systemic therapy.

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

• Histologically confirmed PTCL NOS, angioimmunoblastic T-cell lymphoma, extranodal NK/T-cell lymphoma nasal type, enteropathy- type T-cell lymphoma, subcutaneous panniculitis-like T-cell T-cell lymphoma, hepatosplenic T-cell lymphoma, ALCL??lymphoma, cutaneous (ALK-1 negative), or patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after ASCT;
• Age =18 years;
• Written informed consent
• PD following at least one systemic therapy or refractory to at least one prior systemic therapy;
• Measurable disease according to the IWC criteria and/or measurable cutaneous disease;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Serum potassium = 3.8 mmol/L and magnesium =0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria);
• Negative urine or serum pregnancy test on females of childbearing potential; and
• All women of childbearing potential must use an effective barrier method of contraception (either an intrauterine contraceptive device [IUCD] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter. Male patients should use a barrier method of contraception 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) should be avoided due to a potential drug interaction.

Patients are ineligible for entry if any of the following criteria are met:

• Known central nervous system (CNS) lymphoma [computed tomography (CT) or magnetic resonance imaging (MRI) scans are required only if brain metastasis is suspected clinically];
• Chemotherapy or immunotherapy within 4 weeks of study entry (6 weeks if nitrosoureas given);
• Concomitant use of any other anti-cancer therapy;
• Concomitant use of any investigational agent;
• Use of any investigational agent within 4 weeks of study entry;
• Any known cardiac abnormalities such as:
  • Congenital long QT syndrome;
  • QTcF interval >480 milliseconds (msec);
  • A myocardial infarction within 12 months of study entry;
  • 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).
  • A history of coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present;
  • 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;
  • 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);
  • Uncontrolled hypertension, i.e., blood pressure (BP) of =160/95; or
  • Any cardiac arrhythmia requiring anti-arrhythmic medication;
• Serum potassium <3.8 mmol/L or serum magnesium <0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria);
• Concomitant use of drugs that may cause a prolongation of the QTcF;
• Concomitant use of CYP3A4 inhibitors;
• Concomitant use of warfarin due to a potential drug interaction;
• Clinically significant active infection;
• Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C;
• 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;
• Major surgery within 2 weeks of study entry;
• Previous allogeneic stem cell transplant;
• 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 × 109 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)];
  • Platelet count <100 × 109 cells/L or platelet count <75 × 109 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;
  • 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
  • Serum creatinine >2.0 × ULN;
• Patients who are pregnant or breast-feeding;
• Coexistent second malignancy or history of prior malignancy within previous 5 years (excluding basal or squamous cell carcinoma of the skin, and in situ carcinoma of the cervix (CIN 1) that has been treated curatively);
• Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures; or
• Prior exposure to romidepsin (other HDAC inhibitors are allowed).

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