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

Phase 2

Terminated

• Conditions: Multiple Myeloma

• Registration Number: NCT00431340
• Lead Sponsor: Valerio Therapeutics

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-02-02
• Study First Submitted QC: 2007-02-02
• Study First Posted: 2007-02-05
• Study Start: 2007-03
• Primary Completion: 2007-06
• Study Completion: 2007-06
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-07
• Last Update Posted: 2015-07-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Duration of response, time to response (TTR), and time to progression (TTP).
Effect on biomarkers of bone metabolism. Effect on disease-related bone pain.

Trial Locations

Locations (3)

Oncotherapeutics; 🇺🇸 West Hollywood, California, United States

Center for cancer and blood disorders; 🇺🇸 Bethesda, Maryland, United States

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States