study to assess maximum tolerated dose (MTD), safety, tolerability and activity of IGEV (Ifosfamide, Gemcitabine,Vinorelbine, Prednisolone) + Panobinostat new combination in order to determine the recommended phase II dose

Patients will received 4 p-IGEV courses repeated every 3 weeks in the absence of unacceptable toxicity, whenever an objective response is observed at disease evaluation performed after II cycle.

Eligible patients will be accrued in cohorts of 3 patients at each dose level and dose escalation will be performed following the standard 3+3 rule.

Three patients will be treated for each dose-level, starting from level 1, for one cycle: if no dose-limiting toxicities (DLTs) will be recorded after the first cycle, treatment will be continued in those patients until study completion or unacceptable toxicity and three new patients will be treated at the next dose level. However, if one out of 3 patients will develop a DLT, the same dose-level will be administered to three additional patients for one cycle. If no one of those additional patients will experience a DLT, dose escalation will continue. If more than one over 3 or 6 patients will develop a DLT after the first cycle in any cohort, MTD will be reached. Six further patients will be treated at the lower dose in order to obtain more information about the optimal dose for phase II trials and to characterize pharmacokinetic profiles of this combination. If DLT will be found at level 1 (20 mg), 3 patients will be treated at dose -1 (10 mg). If no more than 1 patient experience toxicity, other 3 patients will be treated to assess more information about pharmacokinetic profiles and safety.

Inclusion Criteria:

• Diagnosis of relapsed or refractory classical HL
• Measurable disease
• One or two prior systemic lines of treatment
• PS(ECOG) 0-2
• Absence of bone marrow infiltration
• Adequate laboratory values for bone marrow, liver and renal functionality

Exclusion Criteria:

• prior or concurrent treatment with a DAC inhibitor including panobinostat
• valproic acid therapy for any medical condition during the study or within 5 days prior to the first panobinostat treatment
• previous autologous hematopoietic stem cell transplant
• other concurrent therapy intended to treat the primary cancer including chemotherapy, investigational or biologic agents or other antitumor agents
• impaired cardiac function or unstable AF
• known history of HIV seropositivity, chronic hepatitis, or other active viral infections
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
• pregnant or breast feeding women