To explore the tolerance and activity of increasing doses of Panobinostat when given in combination with Bortezomib, Cyclophosphamide and Dexamethasone to patients with symptomatic Multiple Myeloma who have had no previous treatment.

Exclusion Criteria29

• Patient has shown intolerance to dexamethasone or cyclophosphamide or components of these drugs
• Patient has greater than 2 grade peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination within 14 days before randomization
• Patient needing valproic acid for any medical condition during the study or within 5 days prior to first administration of panobinostat/study treatment.
• Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted)
• Patient has secondary primary malignancy less than 3 years before first dose of study treatment (except for treated basal or squamous cell carcinoma, or in situ cancer of the cervix).
• Patient who received prior anti-myeloma chemotherapy or medication including IMiDs prior to start of study.
• Patient who received experimental therapy or biologic immunotherapy including monoclonal antibodies less than 4 weeks prior to start of study.
• Prior radiation therapy less than 4 weeks or limited field radiotherapy less than 2 weeks prior start of study or the patient has not recovered from all therapy-related toxicities associated with radiation treatments to < grade 2 CTCAE.
• Patient has undergone major surgery less than 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to < grade 2 CTCAE
• Patients with evidence of mucosal or internal bleeding
• Patient has unresolved diarrhea less than CTCAE grade 2
• Patient has impaired cardiac function, including any one of the following:
• a.LVEF < LLN of institutional norm, as determined by ECHO
• b.obligate use of a permanent cardiac pacemaker
• c.congenital long QT syndrome
• d.history or presence of ventricular tachy-arrhythmias
• e.resting bradycardia defined as < 50 beats per minute
• f.QTcF > 450 msec on screening ECG
• g.complete left bundle branch block (LBBB), bifascicular block
• h.any clinically significant ST segment and/or T-wave abnormalities
• j.myocardial infarction or unstable angina pectoris less than 6 months prior to starting study drug
• k.symptomatic congestive heart failure (New York Heart Association class III-IV)
• l.other clinically significant heart disease and vascular disease (e.g. uncontrolled hypertension
• m.Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pointes, if such treatment cannot be discontinued or switched to a different medication prior to starting study drug.
• Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g. ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
• Patient has any other concurrent severe and/or uncontrolled medical conditions (e.g.,uncontrolled diabetes, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause, uncontrolled thyroid dysfunction) that could cause unacceptable safety risks or compromise compliance with the protocol
• Patient has a known history of HIV seropositivity or history of active/treated hepatitis B or C (a test for screening is not required)
• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double method of contraception during the study and 3 months after the study evaluation completion treatment, of which one must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e.patient has had menses at any time in the preceding 12 consecutive months.
• Patient is a male not willing to use a barrier method of contraception (a condom) during the study and for 3 months after the study evaluation completion treatment