A Trial of Romidepsin for Progressive or Relapsed Peripheral T-cell Lymphoma

• Status: Completed
• Trial end date: 2018-05-17
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celgene; Celgene Corporation
• Treatments: Romidepsin

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).