Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma

Exclusion Criteria

• •1. Primary refractory disease (patients that never reached at least an MR for over 60 days under any prior therapy)
• •2. Patients who have a history of prior MM treatment with a DAC inhibitor including panobinostat
• •3. Patients who have had prior allogeneic stem cell transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy
• •4. Peripheral neuropathy ≥ CTCAE grade 2
• •5. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to the first administration of study drug / treatment or who cannot be switch to safely to alternative anti-epileptic medication
• •6. Patients who have impaired cardiac function including any of the following:
• •* Congenital long QT syndrome, complete left bundle branch block or use of a permanent cardiac pacemaker, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (\< 50 beats per minute). Right bundle branch block + left anterior hemiblock (bifascicular block)
• •* QTcF \> 450 msec on screening ECG
• •* Previous history of angina pectoris or acute MI within 6 months
• •* Congestive heart failure (New York Heart Association functional classification III-IV)
• •* Patient has any other clinically significant cardiovascular disease (e.g. uncontrolled hypertension)
• •7. Patient has an 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 significant small bowel resection)
• •8. Patient has unresolved diarrhea ≥ CTCAE grade 2
• •9. Patients who have any other concurrent severe and/or uncontrolled medical condition(s) including, but not limited to: uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease (e.g. dyspnea at rest from any cause), symptomatic thyroid dysfunction, significant bleeding tendency, that could cause unacceptable safety risks or compromise compliance with the protocol
• •10. Patients who are using medications that have a known relative risk of prolonging the QT interval or of inducing Torsade de Pointes, where such treatment cannot be discontinued or switched to a different medication prior to starting study drug
• •11. Women who are pregnant or breast feeding
• •12. Patients with evidence of another malignancy not in remission or history of such a malignancy within the last 5 years (except for treated basal or squamous cell carcinoma, or in situ cancer of the cervix)
• •13. Patients who have received prior to starting study treatment either radiation therapy to \> 30% of marrow-bearing bone within 4 weeks; myelotoxic chemotherapy within 4 weeks; or immunotherapy within 8 weeks; or who have not yet recovered from side effects of such therapies
• •14. Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff
• •15. Use of chemo-, biologic or immunologic therapy and/or other investigational agents while the patient is on study treatment.
• •16. Patient taking any anti-cancer therapy concomitantly (bisphosphonates are permitted only if commenced prior to the start of screening period)