Trial of Romidepsin and Bortezomib for Multiple Myeloma

Inclusion Criteria Patients must fulfill all of the following criteria to be eligible for study participation: * Male or female patients aged ≥ 18 years old * Has given voluntary written informed consent before any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care * Previously diagnosed with multiple myeloma (MM) based on standard criteria as follows: * Major criteria: 1. Plasmacytomas on tissue biopsy. 2. Bone marrow plasmacytosis (\>30% plasma cells). 3. Monoclonal immunoglobulin spike on serum electrophoresis IgG \>3.5 g/dL or IgA \>2.0 g/dL; kappa or lambda light chain excretion \>1 g/day on 24 hour urine protein electrophoresis * Minor criteria: 1. Bone marrow plasmacytosis (10 to 30% plasma cells) 2. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria 3. Lytic bone lesions. 4. Normal IgM \<50 mg/dL, IgA \<100 mg/dL or IgG \<600 mg/dL Any of the following sets of criteria will confirm the diagnosis of MM: * Any two of the major criteria * Major criterion 1 plus minor criterion 2, 3, or 4. * Major criterion 3 plus minor criterion 1 or 3. * Minor criteria 1, 2, and 3 or 1, 2, and 4. * Currently has MM with: o Measurable disease, defined as a monoclonal immunoglobulin spike on serum electrophoresis of \>=1 gm/dL and/or urine monoclonal immunoglobulin spike of \>=200 mg/24 hours, or evidence of lytic bone disease * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Life-expectancy \> 3 months * All women of childbearing potential must use an effective barrier method of contraception. Male patients should use a barrier method of contraception during the treatment period and for 3 months thereafter * Patients must meet the following laboratory criteria at Baseline (Day 1 of Cycle 1, before study drug administration): * Platelet count ≥ 100\*10\^9/L * Absolute neutrophil count ≥ 1.5\*10\^9/L * OR if the bone marrow is extensively infiltrated * Platelet count ≥ 75\*10\^9/L * Absolute neutrophil count ≥ 1.0\*10\^9/L * Patients must meet the following laboratory criteria at the Screening visit conducted within 14 days of enrollment (Day 1, Cycle 1): * o Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤ 3.0\*upper limit of normal (ULN) * Serum bilirubin ≤ 2.0\*ULN * Calculated or measured creatinine clearance: ≥30 mL/minute. Patient with a creatinine \>10mL/min and \<30 mL/min due to significant myelomatous involvement of the kidneys may be enrolled in the study after receipt of approval from the lead investigator and sponsor * Serum potassium ≥ 3.8 mmol/L * Serum magnesium \>1.8 mg/dL * Serum phosphorus ≥ lower limit of normal (LLN) Exclusion Criteria Patients are ineligible for entry if any of the following criteria are met: * Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or thalidomide, lenalidomide, arsenic trioxide, bortezomib, or glucocorticosteroids within 3 weeks prior to the first dose of romidepsin * Prior major surgery within 3 weeks prior to the first day of treatment * Use of any investigational agent within 4 weeks of study entry * Prior therapy with romidepsin * Any known cardiac abnormalities such as: * Congenital long QT syndrome; * QTc interval ≥ 500 milliseconds; * Myocardial infarction within 6 months of Day 1. Subjects with a history of myocardial infarction between 6 and 12 months prior to the first day of cycle one who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate; * Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min); * Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present; * An ECG recorded at screening showing evidence of cardiac ischemia (ST depression depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present; * Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction \<40% by Multi Gated Acquisition Scan (MUGA scan) or \<50% by echocardiogram and/or MRI; * A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD); * Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes; * Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or * Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers) * POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes) * Plasma cell leukemia * Primary amyloidosis * Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix) * Severe hypercalcemia, i.e., serum calcium ≥14 mg/dL (3.5 mmol/L) * Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C * Other concurrent severe and/or uncontrolled medical or psychiatric conditions. * Concomitant use of drugs that may cause a prolongation of the QTc * Concomitant use of CYP3A4 inhibitors * Patients who have hypersensitivity to bortezomib, boron or mannitol * Patients who are pregnant or breast-feeding * 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