Inclusion Criteria

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part of normal medical care, with the understanding that consent may be withdrawn by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