A Study to Assess BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients
Information source: Novartis
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Myeloma Bone Disease
Intervention: BHQ880 (Drug); Zoledronic acid (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Novartis Pharmaceuticals Official(s) and/or principal investigator(s): Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals
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.
Clinical Details
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
Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Time to first SRE and change in bone markers for bone resorption and formation
Secondary outcome: Characterize acute and chronic safety and tolerability of BHQ880Characterize single-dose and repeated-dose pharmacokinetic profiles of BHQ880 Assess the potential immunogenicity of BHQ880 Characterize the binding kinetics of DKK1/BHQ880 complex (free and BHQ880 bound DKK1) in serum Determine the pharmacodynamic effects of BHQ880 by measuring biochemical markers of bone formation, resorption, and metabolism in serum and urine
Detailed description:
The study was originally planned to have two phases. Phase II, the dose expansion phase, was
not conducted.
Eligibility
Minimum age: 18 Years.
Maximum age: 78 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Relapsed or refractory multiple myeloma patients requiring treatment with a
non-bortezomib-containing regimen (prior treatment with bortezomib is acceptable)
• The diagnosis of symptomatic multiple myeloma (International Myeloma Working Group)
2. Patients with multiple myeloma who do not have measurable serum M-protein or
measurable urine M-protein must have measurable increased concentrations of free
light chains (using FreeLite™)
3. At least one prior SRE defined as one of the following:
- Pathologic fracture
- Spinal cord compression
- Requirement for either radiation or surgery to bone due to:
- Pain
- Prevention of imminent fracture
- Stabilization of a fracture
4. Current or planned treatment with zoledronic acid
5. Ambulatory patients aged 18 years or older
6. Adequate organ function
Exclusion Criteria:
1. Known concomitant disease(s) known to influence calcium metabolism including
hyperparathyroidism, hyperthyroidism and/or Paget's disease of bone.
2. Current active dental problems including
- Ongoing infection of the teeth or jawbone (maxilla or mandibula)
- Current exposed bone in the mouth
- Dental or fixture trauma
- Current or previous osteonecrosis of the jaw
- Slow healing after dental procedures
- Recent (within 6 weeks) or planned dental or jaw surgery during the study
(extraction, implants)
3. Patients who are allergic to/ intolerant of bisphosphonate therapy
4. Other concurrent severe and/or uncontrolled concomitant medical conditions (e. g.
uncontrolled diabetes, active or uncontrolled infection, uncontrolled diarrhea) that
could cause unacceptable safety risks or compromise compliance with the protocol
5. Other clinically significant heart disease (e. g. symptomatic congestive heart
failure, uncontrolled arrhythmia, uncontrolled hypertension, history of labile
hypertension, or history of poor compliance with an antihypertensive regimen)
Other protocol-defined inclusion/exclusion criteria may apply
Locations and Contacts
Novartis Investigative Site, Bradford BD9 6RJ, United Kingdom
Novartis Investigative Site, London EC1A 7BE, United Kingdom
Novartis Investigative Site, London SE1 9RT, United Kingdom
Novartis Investigative Site, Manchester M20 4BX, United Kingdom
Mayo Clinic - Arizona Cancer Clinical Research Unit, Scottsdale, Arizona 85259, United States
Highlands Oncology Group Dept of Highlands Oncology Grp, Fayetteville, Arkansas 72703, United States
Dana Farber Cancer Institute Deptof DanaFarberCancerInst(2), Boston, Massachusetts 02115, United States
MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (11), Houston, Texas 77030-4009, United States
Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(4), San Antonio, Texas 78229, United States
Additional Information
Starting date: January 2009
Last updated: February 15, 2013
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