Study of Pomalidomide, Dexamethasone, and Romidepsin for Rel/Ref Myeloma

Inclusion Criteria: * histologically confirmed multiple myeloma. * measurable disease as defined by \> 0.5 g/dL serum monoclonal protein, \>0.1 g/dL serum free light chains, \>0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s). * relapsed or refractory multiple myeloma as defined by progression of disease either after prior therapy or lack of response to currently used therapy * relapsed or progressive disease after at least 3 prior therapeutic treatments or regimens for multiple myeloma. * refractory to bortezomib and lenalidomide * \>18 years at the time of signing the informed consent form. * life expectancy of \> 3 months. * Karnofsky performance status \> 70%, or \> 60% if due to bony involvement of multiple myeloma * normal organ and marrow function as defined below: 1. Absolute Neutrophil Count \> 1,000 cells/mm3 for Phase I, \> 750 cells/mm3 for Phase II 2. Platelet Count \> 75,000/mm3 for Phase I, \> 50, 000/mm3 for Phase II 3. AST/ Serum SGOT \< 3.0 x upper limits of normal 4. ALT/ Serum SGPT \< 3.0 x upper limit of normal 5. Serum creatinine \< 2.0 mg/dL 6. Serum total bilirubin \< 1.5 x upper limit of normal * Laboratory test results within these ranges: g. Serum potassium ≥ 3.8 mmol/L h. Serum magnesium \>1.8 mg/dL * Females of child bearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to start of study drug(s) and again with 24 hours of prescribing pomalidomide (prescriptions must be filled within 7 days). * Females of child bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before starting pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. * able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin). * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Subjects with non-secretory Multiple Myeloma (no measurable monoclonal protein or plasmacytoma(s), free light chains, and/or M-spike in blood or urine). * Patients with a prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 3 years. * Any known cardiac abnormalities such as: 1. Congenital long QT syndrome 2. QTc interval ≥ 480 milliseconds 3. Myocardial infarction within 6 months of C1D1. Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 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 4. Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) 5. Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV. In any subject in whom there is doubt, the subject should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present 6. 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 7. Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Appendix E) and/or ejection fraction \<40% by MUGA scan or \<50% by echocardiogram and/or MRI; 8. 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); 9. Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes; 10. 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 11. Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers) * Any Known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. * Any active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program. * Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial. * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking pomalidomide.) * Subjects with any condition, including the presence of laboratory abnormalities, which in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Use of any other experimental drug or therapy within 14 days of baseline. * Subjects with a history of development of erythema nodosum, if characterized by a desquamating rash, while taking thalidomide, lenalidomide, pomalidomide or similar drugs. * Concurrent use of other anti-cancer agents or treatment. * Concomitant use of CYP3A4 inhibitors (See Appendix D) * Prior therapy with romidepsin, thalidomide or pomalidomide * Central nervous system or meningeal involvement * Patients taking drugs leading to significant QT prolongation * Known hypersensitivity to thalidomide or lenalidomide