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

Study Overview
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Brief Summary
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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.

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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: PXD101


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: PXD101|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate of belinostat administered in combination with bortezomib in multiple myeloma subjects who are refractory to or have relapsed from at least one prior bortezomib-containing regimen. |  |  | 
| Safety of belinostat plus bortezomib. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response, time to response (TTR), and time to progression (TTP). |  |  | 
| Effect on biomarkers of bone metabolism. Effect on disease-related bone pain. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple myeloma, myeloma, plasma cell myeloma, bone marrow cancer, myelomatosis, Kahler's disease, PXD101, belinostat, bortezomib