Melphalan and Panobinostat (LBH589) for the Treatment of Patients With Recurrent Multiple Myeloma

Inclusion criteria: * Diagnosis of multiple myeloma, based on the following criteria: * Major criteria * Plasmacytomas on tissue biopsy (1) * Bone marrow plasmacytosis (\> 30% plasma cells) (2) * Monoclonal immunoglobulin (Ig) spike on serum electrophoresis, IgG \> 3.5 g/dL or IgA \> 2.0 g/dL, and kappa or lambda light chain excretion \> 1 g/day on 24-hour urine protein electrophoresis (3) * Minor Criteria * Bone marrow plasmacytosis (10-30% plasma cells) (a) * Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria (b) * Lytic bone lesions ©) * Normal IgM \< 50 mg/dL, IgA \< 100 mg/dL, or IgG \< 600 mg/dL (d) * Meets any of the following sets of multiple myeloma diagnostic criteria: * Any two of the major criteria * Major criterion 1 plus minor criterion b, c, or d * Major criterion 3 plus minor criterion a or c * Minor criteria a, b, and c, OR a, b, and d * Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of ≥ 1 g/dL and/or urine monoclonal immunoglobulin spike of ≥ 200 mg/24 hours, or evidence of lytic bone disease * Must have received ≥ 1 prior treatment regimen OR refractory to most recent chemotherapy * Relapsed following stabilization or response to standard first-line chemotherapy (e.g., vincristine, doxorubicin hydrochloride, and prednisone or melphalan and prednisone) or first-line high-dose chemotherapy * Refractory (i.e., failure to achieve at least complete or partial response or stable disease) to most recent chemotherapy, whether or not containing systemic corticosteroids * Prior treatment with ≤ 4 days of a total of 400 mg of prednisone (or an equivalent potency of another steroid) for myeloma is not considered a regimen * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Life expectancy \> 3 months * Platelet count ≥ 75 x 10\^9/L (≥ 50 x 10\^9/L if bone marrow is extensively infiltrated) * Absolute neutrophil count ≥ 1.5 x 10\^9/L (≥ 1.0 x 10\^9/L if bone marrow is extensively infiltrated) * Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 times upper limit of normal (ULN) * Serum bilirubin ≤ 1.5 times ULN * Creatinine clearance ≥ 30 mL/min; creatinine \> 10 mL/min and \< 30 mL/min due to significant myelomatous involvement of the kidneys allowed with medical director approval * Serum potassium ≥ lower limit of normal (LLN) * Serum magnesium ≥ LLN * Serum phosphorus ≥ LLN * Prior localized radiotherapy Exclusion criteria: * Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS syndrome) * Plasma cell leukemia * Pregnant or nursing females; fertile patients must use effective contraception * Peripheral neuropathy \> grade 2 * Impaired cardiac function or clinically significant cardiac disease (including congenital long QT syndrome, history or presence of sustained ventricular tachyarrhythmia; history of ventricular fibrillation or Torsade de Pointes; bradycardia, defined as heart rate (HR) \< 50 beats per minute (bpm) \[pacemaker allowed provided HR ≥ 50 bpm\]; corrected QT interval \> 450 msec on screening ECG; left ventricular ejection fraction below normal on screening ECHO or multigated acquisition (MUGA) scan; right bundle branch block with left anterior hemiblock (bifascicular block); myocardial infarction or unstable angina within the past 6 months; New York Heart Association class III-IV congestive heart failure; uncontrolled hypertension; history of labile hypertension; history of poor compliance with an antihypertensive regimen) * Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat * Prior malignancy within the past 5 years except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix * Other concurrent severe and/or uncontrolled medical or psychiatric conditions (e.g., uncontrolled diabetes or active or uncontrolled infection), including abnormal laboratory values that could cause unacceptable safety risks or compromise protocol compliance * Known positivity for HIV or hepatitis B or C * Severe hypercalcemia (i.e., serum calcium ≥ 14 mg/dL) * Significant history of non-compliance to medical regimens or unwillingness or inability to comply with instructions given by the study staff * Concurrent medication that risk prolonging the QT interval or inducing Torsades de Pointes * Prior panobinostat * Received chemotherapy, bortezomib, thalidomide, lenalidomide or arsenic trioxide within 3 wks of enrollment (with the exception of nitrosoureas within 6 wks of enrollment) * Received corticosteroids (\>10 mg/day prednisone or equivalent) within three weeks before enrollment. * Received immunotherapy within \< 8 weeks; antibody within \< 4 weeks; or radiation therapy to \> 30% of marrow-bearing bone within \< 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.