A Study to Assess BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients
This study has been completed.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00741377
First received: August 22, 2008
Last updated: February 15, 2013
Last verified: February 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Multiple Myeloma Bone Disease |
Drug: BHQ880 Drug: Zoledronic acid |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Time to first SRE and change in bone markers for bone resorption and formation [ Time Frame: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Characterize acute and chronic safety and tolerability of BHQ880 [ Time Frame: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy ] [ Designated as safety issue: Yes ]
- Characterize single-dose and repeated-dose pharmacokinetic profiles of BHQ880 [ Time Frame: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy ] [ Designated as safety issue: Yes ]
- Assess the potential immunogenicity of BHQ880 [ Time Frame: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy ] [ Designated as safety issue: Yes ]
- Characterize the binding kinetics of DKK1/BHQ880 complex (free and BHQ880 bound DKK1) in serum [ Time Frame: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy ] [ Designated as safety issue: Yes ]
- Determine the pharmacodynamic effects of BHQ880 by measuring biochemical markers of bone formation, resorption, and metabolism in serum and urine [ Time Frame: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy ] [ Designated as safety issue: Yes ]
| Enrollment: | 28 |
| Study Start Date: | January 2009 |
| Study Completion Date: | December 2011 |
| Primary Completion Date: | December 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: BHQ880 + zoledronic acid
BHQ880 3-40 mg/kg in combination with zoledronic acid 4 mg on day 1 of a 28-day cycle.
|
Drug: BHQ880
Drug: Zoledronic acid
Other Name: ZOL446
|
Detailed Description:
The study was originally planned to have two phases. Phase II, the dose expansion phase, was not conducted.
Eligibility| Ages Eligible for Study: | 18 Years to 78 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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)
- 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™)
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
- Current or planned treatment with zoledronic acid
- Ambulatory patients aged 18 years or older
- Adequate organ function
Exclusion Criteria:
- Known concomitant disease(s) known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism and/or Paget's disease of bone.
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)
- Patients who are allergic to/ intolerant of bisphosphonate therapy
- 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
- 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00741377
Locations
| United States, Arizona | |
| Mayo Clinic - Arizona Cancer Clinical Research Unit | |
| Scottsdale, Arizona, United States, 85259 | |
| United States, Arkansas | |
| Highlands Oncology Group Dept of Highlands Oncology Grp | |
| Fayetteville, Arkansas, United States, 72703 | |
| United States, Massachusetts | |
| Dana Farber Cancer Institute Deptof DanaFarberCancerInst(2) | |
| Boston, Massachusetts, United States, 02115 | |
| United States, Texas | |
| MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (11) | |
| Houston, Texas, United States, 77030-4009 | |
| Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(4) | |
| San Antonio, Texas, United States, 78229 | |
| United Kingdom | |
| Novartis Investigative Site | |
| Bradford, United Kingdom, BD9 6RJ | |
| Novartis Investigative Site | |
| London, United Kingdom, SE1 9RT | |
| Novartis Investigative Site | |
| London, United Kingdom, EC1A 7BE | |
| Novartis Investigative Site | |
| Manchester, United Kingdom, M20 4BX | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT00741377 History of Changes |
| Other Study ID Numbers: | CBHQ880A2102, 2008-000411-15 |
| Study First Received: | August 22, 2008 |
| Last Updated: | February 15, 2013 |
| Health Authority: | United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration |
Keywords provided by Novartis:
|
Multiple myeloma bone disease antibody |
Additional relevant MeSH terms:
|
Bone Diseases Multiple Myeloma Neoplasms, Plasma Cell Musculoskeletal Diseases 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 Zoledronic acid Diphosphonates Bone Density Conservation Agents Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 22, 2013