A Phase II Study of Belinostat in Combination With Bortezomib in Patients With Relapsed, Refractory Multiple Myeloma

A Phase II Study of Belinostat in Combination With Bortezomib in Patients With Relapsed, Refractory Multiple Myeloma

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.

Inclusion Criteria:

• 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.