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consent before any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care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)
• •* 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