Oral Panobinostat Adult Patients DLBCL Relapsed/Refractory Stem Cell Transfusion (ASCT) or Not Eligible for ASCT

Inclusion Criteria

• Patient age is ≥ 18 years
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Patient has a history of DLBCL according to the WHO classification
• Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen, standard second line therapy (DHAP, ESHAP, ICE or similar salvage regimens) inclusive ASCT
• Patient has progressive disease after receiving at least CHOP-R or CHOP-R like first line regimen and is not considered eligible for intensive salvage therapy including ASCT because of age, co-morbidities, impossibility to perform ASCT
• Patient undergoes at baseline new lymphnode or other pathologic tissue biopsy for confirmation of diagnosis and biologic studies; bone marrow biopsy is not adequate for this purpose and should be performed only for staging. Patients with primary refractoriness, not eligible for intensive salvage therapy including ASCT, who performed a previous biopsy with stored frozen material 6 months or less before enrolment into the study do not have to repeat a new biopsy
• Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible, but this criteria alone should not be used for disease measurement
• Patient has the following laboratory values (labs may be repeated, if needed, to obtain acceptable values before screen fail):
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L [SI units 1.5 x 109/L]
• Platelet count ≥ 100 x 109/L
• Serum potassium, magnesium, phosphorus, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution
• Serum creatinine ≤ 1.5 x ULN
• Serum bilirubin ≤ 1.5 x ULN (or ≤ 3.0 x ULN, if patient has Gilbert syndrome)
• AST/SGOT and/or ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
• Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
• Written informed consent was obtained from the patient prior to any study-specific screening procedures
• Patient has the ability to swallow capsules or tablets
• Practice acceptable birth control.

Exclusion Criteria

• Patient has a history of prior treatment with a DAC inhibitors including panobinostat
• Patient will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment
• Patient has been treated with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment
• Patient has been treated with any other anti lymphoma therapy within 3 weeks of start of study treatment
• Patient is using any anti-cancer therapy concomitantly
• Patient has been treated with > 5 prior systemic lines of treatment
• Patient has received prior radiation therapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to start of study treatment
• Patient treated with allogeneic hematopoietic stem cell transplant with active progressive cGVHD; patient has received DLI ≤ 6 weeks prior to start of study treatment; patient is planned to receive DLI
• Patient has a history of another malignancy ≤ 3 years before study entry, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine cervix
• Patient has a history of CNS involvement with lymphoma
• Patient has impaired cardiac function including any of the following:
• Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia ( 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
• Presence of unst