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

• Status: Completed
• Trial end date: 2014-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether intravenous Bortezomib combined with oral Panobinostat (LBH589) are effective in treating adult patients with relapsed/refractory peripheral T-cell lymphoma or NK/T-cell lymphoma after the failure of conventional chemotherapy.

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

Details

• Lead Sponsor: Singapore General Hospital
• Treatments: Bortezomib; Histone Deacetylase Inhibitors; Panobinostat

Criteria

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