Study of Bortezomib and Panobinostat in Treating Patients With Relapsed/Refractory Peripheral T-cell Lymphoma or NK/T-cell Lymphoma

This is an interventional treatment trial for Peripheral T-cell Lymphoma (Not Otherwise Specified) focused on measuring t-cell lymphoma, peripheral t-cell lymphoma, nk/t-cell lymphoma, nasal type, bortezomib, velcade, panobinostat, LBH589b, histone deacetylase inhibitor, proteasome inhibitor Read More

Inclusion Criteria:

• Histologically confirmed PTCL NOS, angioimmunoblastic T-cell lymphoma, extranodal NK/T-cell lymphoma nasal type, enteropathy- type T-cell lymphoma, hepatosplenic T-cell lymphoma, ALCL (ALK-1 negative), or patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after ASCT
• Age ≥21 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 IWC criteria and/or measurable bone marrow disease by flow cytometry or morphology
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count of ≥1000 × 10(9)cells/L
• 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
• All females of childbearing potential and males must use an effective barrier method of contraception during the treatment period and for at least 1 month thereafter.

Exclusion Criteria:

• Chemotherapy or immunotherapy within 3 weeks of study entry
• Concomitant use of any other anti-cancer therapy
• Concomitant use of any other investigational agent

• 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 < 50 beats/ min).
  • 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);
  • 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
• Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule
• Concomitant use of warfarin due to a potential drug interaction
• Clinically significant active infection
• Known infection with human immunodeficiency virus (HIV)
• Patient has known clinically active hepatitis B or 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 stem cell transplant
• Major surgery within 2 weeks of study entry
• Peripheral neuropathy or neuropathic pain of Grade 2 or worse
• Platelet count <50 × 109 cells/L or platelet count <30 × 109 cells/L if bone marrow disease involvement is documented
• Serum creatinine >2.0 × ULN
• Patients who are pregnant or breast-feeding
• Patient has known hypersensitivity to any components of bortezomib (such as boron, mannitol), or panobinostat