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

This study has been terminated.
(Terminated due to dose limiting toxicity)
Sponsor:
Information provided by (Responsible Party):
TopoTarget A/S
ClinicalTrials.gov Identifier:
NCT00431340
First received: February 2, 2007
Last updated: November 29, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: PXD101
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Belinostat in Combination With Bortezomib in Patients With Relapsed, Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by TopoTarget A/S:

Primary Outcome Measures:
  • 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:
  • Duration of response, time to response (TTR), and time to progression (TTP).
  • Effect on biomarkers of bone metabolism. Effect on disease-related bone pain.

Enrollment: 4
Study Start Date: March 2007
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00431340

Locations
United States, California
Oncotherapeutics
West Hollywood, California, United States, 90069
United States, Maryland
Center for cancer and blood disorders
Bethesda, Maryland, United States, 20817
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
TopoTarget A/S
Investigators
Principal Investigator: James Berenson, MD James R. Berenson, MD, Inc.
  More Information

No publications provided

Responsible Party: TopoTarget A/S
ClinicalTrials.gov Identifier: NCT00431340     History of Changes
Other Study ID Numbers: PXD101-CLN-16
Study First Received: February 2, 2007
Last Updated: November 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by TopoTarget A/S:
Multiple myeloma
myeloma
plasma cell myeloma
bone marrow cancer
myelomatosis
Kahler's disease
PXD101
belinostat
bortezomib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014