Panobinostat Maintenance Therapy in Treating Patients with Multiple Myeloma after Stem Cell Transplant

Inclusion Criteria

• RESEARCH SAMPLE COLLECTION: Histologically confirmed diagnosis of multiple myeloma
• RESEARCH SAMPLE COLLECTION: Considered for high-dose melphalan followed by autologous hematopoietic cell transplantation and undergoing pre-HCT workup
• PANOBINOSTAT MAINTENANCE INCLUSION
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Histologically confirmed diagnosis of multiple myeloma
• Meeting the criteria for symptomatic multiple myeloma (hypercalcemia renal [kidney] impairment, anemia, bone lesions "[CRAB]” criteria) before the initiation of systemic chemotherapy
• Received high-dose melphalan (>= 140 mg/m^2) followed by autologous HCT based on the institutional guidelines and within +45 and +180 after autologous HCT at the time of panobinostat maintenance initiation
• Patients must have achieved at least partial response (PR) prior to autologous HCT and must not have progressive disease (PD) prior to the initiation of maintenance therapy
• Absolute neutrophil count (ANC) >= 1 x 10^9/L
• Hemoglobin >= 8 g/dl
• Platelets >= 50 x 10^9/L (without transfusion support)
• Creatinine clearance >= 40 ml/min or serum creatinine =< 2.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Serum bilirubin =< 1.5 x ULN
• Albumin > 3.0 g/dl
• Clinically euthyroid; Note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
• Baseline (pre-HCT) multi-gated acquisition (MUGA) or echocardiography (ECHO) must demonstrate left ventricular ejection fraction (LVEF) >= the lower limit of normal (LLN) of the institutional normal
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 or Karnofsky performance status >= 70%
• Prior histone deacetylase (HDAC), deacetylase (DAC), heat shock protein (HSP)90 inhibitors or valproic acid for the treatment of cancer is allowed

Exclusion Criteria

• RESEARCH SAMPLE COLLECTION: Myeloma patients who are not candidates for high-dose melphalan followed by autologous HCT based on institutional standards
• PANOBINOSTAT MAINTENANCE EXCLUSION
• Patients who have purely non-secretory multiple myeloma (i.e., the absence of a measurable protein in serum by electrophoresis and immunofixation and the absence of Bence-Jones protein in the urine defined by use of electrophoresis and immunofixation)
• Prior allogeneic HCT
• Prior solid organ transplant requiring immunosuppressive therapy
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• 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 Novartis 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) * Patients with 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)
• Patients with diarrhea > Common Terminology Criteria for Adverse Events (CTCAE) grade 2
• 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
• Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Patients who have 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
• Patients who have received either immunotherapy within =< 8 weeks; chemotherapy 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
• Patients who have undergone major surgery =< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control; WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months); women of childbearing potential must have a negative serum pregnancy test within 24hrs of receiving the first dose of study medication
• Male patients whose sexual partners are WOCBP not using effective birth control
• Patients with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
• Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
• 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