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 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 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) 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 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.