Panobinostat, Gemcitabine Hydrochloride, Busulfan, and Melphalan Before Stem Cell Transplant in Treating Patients With Refractory or Relapsed Multiple Myeloma

Inclusion Criteria

• Refractory or relapsed myeloma, defined as one or more of the following:
• Treated with first-line therapy including at least 2 cycles of lenalidomide, bortezomib or thalidomide, and one or more of the following:
• Less than partial response (PR) to first-line therapy
• Relapse after first (1st) line therapy
• High-risk cytogenetics, defined by deletion (del)(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by fluorescence in situ hybridization (FISH)
• Relapse after a prior autologous stem cell transplant (ASCT)
• Plasma cell leukemia
• Soft tissue plasmacytoma
• Serum creatinine = = 50 ml/min
• Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) = = 50% of expected corrected for hemoglobin and/or volume
• Adequate cardiac function with left ventricular ejection fraction >= 40%
• No uncontrolled arrhythmias or symptomatic cardiac disease
• Clinically euthyroid; note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
• Zubrod performance status = 2.5 million cluster of differentiation (CD)34+ cells/kg previously apheresed
• Ability to provide written informed consent

Exclusion Criteria

• Prior whole brain irradiation
• Having received radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment
• Active hepatitis B, either active carrier (hepatitis B surface antigen positive [HBsAg +]) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] >= 10,000 copies/mL, or >= 2,000 IU/mL)
• Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
• Active infection requiring parenteral antibiotics
• Known positivity for human immunodeficiency virus (HIV)
• Autologous stem-cell transplant in the previous six months
• Needing valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Secura Bio, Inc (Secura Bio) prior to enrollment)
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as heart rate (HR) = 50 bpm
• Screening electrocardiogram (ECG) with a corrected QT (QTc) > 470 msec
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Myocardial infarction or unstable angina = 30% of marrow-bearing bone within = = 3 nonhematological toxicity from prior therapy that has not resolved to =< grade 1