A Trial of Romidepsin for Progressive or Relapsed Peripheral T-cell Lymphoma
Condition: Peripheral T-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: Romidepsin
Intervention description: Romidepsin intravenously (through a vein) over 4 hours on Days 1, 8 and 15 of each 28-day cycle.
Intervention MeSH terms: Romidepsin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: peripheral T-cell lymphoma; T-cell lymphoma; romidepsin

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

        Patients must fulfill all of the following criteria to be eligible for study participation
        and have:

          -  Histologically confirmed PTCL not otherwise specified, angioimmunoblastic T-cell
             lymphoma, extranodal natural killer (NK)/T-cell lymphoma nasal type, enteropathy- type
             T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous γδ T-cell
             lymphoma (excludes mycosis fungoides or Sezary syndrome), transformed mycosis
             fungoides, hepatosplenic T-cell lymphoma, anaplastic large cell lymphoma (ALCL;
             anaplastic lymphoma kinase [ALK]-1 negative), or patients with ALK 1 expressing ALCL
             (ALK-1 positive) who have relapsed disease after autologous stem cell transplant
             (ASCT);

          -  Age ≥18 years;

          -  Written informed consent;

          -  Progressive disease following at least one systemic therapy or refractory to at least
             one prior systemic therapy;

          -  Measurable disease according to the International Workshop Response (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.

        Exclusion Criteria:

        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);

          -  Initiation of corticosteroids during study (defined as 7 days prior to Cycle 1 Day
             1[C1D1] until study drug discontinuation)

               -  Patients treated with a pulse of steroids were to discontinue steroid use 7 days
                  prior to C1D1 and have a repeat CT scan and disease assessment after
                  discontinuation of corticosteroids and before starting romidepsin;

          -  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;

               -  QTc interval >480 milliseconds (msec);

               -  A myocardial infarction within 6 months of C1D1. Patients with a history of
                  myocardial infraction 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 participate;

               -  Other significant electrocardiogram (ECG) abnormalities including 2nd degree
                  atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia
                  (ventricular rate less than 50 beats/min).

               -  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;

               -  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; 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;

          -  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 significant prolongation of the QTc;

          -  Concomitant use of CYP3A4 significant or moderate inhibitors;

          -  Concomitant use of therapeutic warfarin or another anticoagulant due to a potential
             drug interaction. Use of a small dose of a anticoagulant to maintain patency of venous
             access port and cannulas is permitted;

          -  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 × 10^9 cells/L [patients with neutropenia
                  (ANC 1-1.5 10^9 cells/L) as a function of their disease may be supported with
                  granulocyte-colony stimulating factor (G-CSF)];

               -  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;

               -  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 solid organ malignancy within
             previous 3 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 prior history of a hematologic malignancy (other than T-cell lymphoma);

          -  Any significant medical or psychiatric condition that might prevent the patient from
             complying with all study procedures; or

          -  Prior exposure to romidepsin (other histone deacetylase inhibitors are allowed).