Multiple Myeloma Bone Disease Clinical Trial
Official title:
A Phase Ib/II Multicenter Dose-determination Study, With an Adaptive, Randomized, Placebo-controlled, Double-blind Phase II, Using Various Repeated IV Doses of BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients With Prior Skeletal-related Event
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.
The study was originally planned to have two phases. Phase II, the dose expansion phase, was not conducted. ;
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment