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 =< 1.8 mg/dL and/or estimated serum creatinine clearance >= 50 ml/min
Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
Serum bilirubin =< 2 x upper limit of normal, unless proven to be due to disease involvement
Alkaline phosphatase =< 2 x upper limit of normal, unless proven to be due to disease involvement
Adequate pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 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
Negative beta-human chorionic gonadotropin (HCG) test in a woman of child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
Availability of >= 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 beats per minute (bpm); patients with pacemakers are eligible if 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 =< 12 months prior to starting study drug
Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
Have undergone major surgery =< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
Prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
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
Received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies
Having received immunotherapy or chemotherapy within 2 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
Grade >= 3 nonhematological toxicity from prior therapy that has not resolved to =< grade 1