A Study to Assess BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients
Status:
Completed
Trial end date:
2011-12-01
Target enrollment:
Participant gender:
Summary
This study has two portions, a phase I portion and a phase II portion. The purpose of the
phase I portion is to assess the maximum-tolerated dose (MTD) and to characterize dose
limiting toxicity (DLT) of escalating doses of BHQ880 (up to a maximum dose of 20 mg/kg) in
combination with standard chemotherapy and zoledronic acid in relapsed or refractory multiple
myeloma patients.
The phase II portion of the study will also be conducted in relapsed or refractory multiple
myeloma patients. Patients will be treated with various doses of BHQ880 or placebo in
combination standard chemotherapy. In the phase II portion of the study zoledronic acid will
be added after the first 28 days of therapy with BHQ880 or placebo and standard chemotherapy.
This will allow any BHQ880-related changes in bone biomarkers to be detected in a zoledronic
acid-free environment. The purpose of the phase II portion of the study, is to determine one
or more doses of BHQ880 for further development based on dose-efficacy modeling. Efficacy is
defined as time to first skeletal-related event and change in bone markers for bone
resorption and formation relative to placebo. A skeletal-related event is defined as:
- Pathologic fracture
- Spinal cord compression
- Requirement for either radiation or surgery to bone due to:
- Pain
- Prevention of imminent fracture
- Stabilization of a fracture Biomarker and imaging endpoints will be assessed in
both phases of the study. The pharmacodynamic effects of BHQ880 will be assessed by
measuring biochemical markers of bone formation, resorption, and metabolism in
serum and urine. Charges in serum DKK1 levels will be characterized. The size and
number of lytic bone lesions as measured by bone survey (X-ray) or MRI will be
assessed. In addition, bone mineral density (BMD) will be measured by DEXA scan and
at selected sites with QCT scans.