This open-label study will assess anti-tumor activity and safety of belinostat in combination with bortezomib (Velcade®) in multiple myeloma patients refractory to or relapsed from at least one prior bortezomib-containing regimen. Subjects will be administered both PXD101 and bortezomib on the same days: i.e. days 1, 4, 8, and 11 of a 3-week cycle, for up to 8 cycles.
Diagnosis of multiple myeloma. Status of refractory to or relapsed from at least one prior bortezomib-containing regimen. Progressive disease. Age >= 18 years. Karnofsky performance status >= 60%
Acceptable liver function:
Bilirubin =< 1.5 x ULN (upper limit of normal) Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3 x ULN
Acceptable hematologic status:
Absolute Neutrophil Count (ANC) >= 1.5 x 109/L Platelet count >= 100 x 109/L Hemoglobin >= 9 g/dL Coagulation status PT-INR/PTT =< 1.5 x ULN or in the therapeutic range if on anticoagulation therapy. (PT-INR/PTT= prothrombin - international normalized ratio / prothrombin time) Serum potassium within normal range. Estimated life expectancy greater than 3 months. Signed, written IRB (institutional Review Board)-approved informed consent.
Exclusion Criteria:
Non-secretory multiple myeloma or symptomatic amyloidosis. Hypersensitivity to bortezomib, boron, or mannitol. Less than 4 weeks since prior chemotherapy, radiotherapy, endocrine therapy, or immunotherapy, except if disease is rapidly progressing. Less than 4 weeks since prior use of other investigational agents. Serious concomitant systemic disorders (e.g. active infection). Significant cardiovascular disease. Marked baseline prolongation of QT/QTc (corrected QT interval)interval. Central nervous system disorders requiring neuroleptics / anti-convulsants. Peripheral sensory neuropathy of ≥ Grade 2 Renal insufficiency defined as a creatinine clearance of < 30 ml/min. Non-willingness to use effective contraceptive methods for patients of child-bearing age / potential. Pregnant or breast-feeding women. Known HIV positivity. Prior treatment with belinostat (PXD101), or any other HDAC (histone deacetylase) inhibitor. Altered mental status which precludes an understanding of the Informed Consent Document.
