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A Study to Assess BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients

Primary Purpose

Multiple Myeloma Bone Disease

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BHQ880

Zoledronic acid

About this trial

This is an interventional treatment trial for Multiple Myeloma Bone Disease focused on measuring Multiple myeloma, bone disease, antibody

Eligibility Criteria

18 Years - 78 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic - Arizona Cancer Clinical Research Unit
Highlands Oncology Group Dept of Highlands Oncology Grp
Dana Farber Cancer Institute Deptof DanaFarberCancerInst(2)
MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (11)
Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(4)
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BHQ880 + zoledronic acid

Arm Description

BHQ880 3-40 mg/kg in combination with zoledronic acid 4 mg on day 1 of a 28-day cycle.

Outcomes

Primary Outcome Measures

Time to first SRE and change in bone markers for bone resorption and formation

Secondary Outcome Measures

Characterize acute and chronic safety and tolerability of BHQ880

Characterize 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

Full Information

NCT ID

NCT00741377

First Posted

August 22, 2008

Last Updated

February 15, 2013

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00741377

Brief Title

A Study to Assess BHQ880 in Combination With Zoledronic Acid in Relapsed or Refractory Myeloma Patients

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 Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Completed

Study Start Date

January 2009 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief 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.

Detailed Description

The study was originally planned to have two phases. Phase II, the dose expansion phase, was not conducted.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma Bone Disease

Keywords

Multiple myeloma, bone disease, antibody

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

28 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BHQ880 + zoledronic acid

Arm Type

Experimental

Arm Description

BHQ880 3-40 mg/kg in combination with zoledronic acid 4 mg on day 1 of a 28-day cycle.

Intervention Type

Drug

Intervention Name(s)

BHQ880

Intervention Type

Drug

Intervention Name(s)

Zoledronic acid

Other Intervention Name(s)

ZOL446

Primary Outcome Measure Information:

Title

Time to first SRE and change in bone markers for bone resorption and formation

Time Frame