Clinical trial NCT00431340: A Phase II Study of Belinostat in Combination With Bortezomib in Patients With Relapsed, Refractory Multiple Myeloma
Official title: A Phase II Study of Belinostat in Combination With Bortezomib in Patients With Relapsed, Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
myeloma
plasma cell myeloma
bone marrow cancer
myelomatosis
Kahler's disease
PXD101
belinostat
bortezomib
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
First posted: 2007-02-05
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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.
measure: Safety of belinostat plus bortezomib.
Secondary outcomes:
measure: Duration of response, time to response (TTR), and time to progression (TTP).
measure: Effect on biomarkers of bone metabolism. Effect on disease-related bone pain.
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: Oncotherapeutics
state: California
city: Bethesda
country: United States
facility: Center for cancer and blood disorders
state: Maryland
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
References: