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Multiple Myeloma Bone DiseasePhase 1NCT00741377

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

A Phase 1 study testing BHQ880 and Zoledronic acid in people with Multiple Myeloma Bone Disease, run by Novartis Pharmaceuticals at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 78 years
Conditions the study is for
Multiple Myeloma Bone Disease
What is being tested?
BHQ880 and Zoledronic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
9 sitesin 2 countries
Study dates
Jan 2009to Dec 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 78 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States5 sites

  • Dana Farber Cancer Institute Deptof DanaFarberCancerInst(2)

    Boston, Massachusetts, 02115

  • Highlands Oncology Group Dept of Highlands Oncology Grp

    Fayetteville, Arkansas, 72703

  • MD Anderson Cancer Center/University of Texas Dept. of MD Anderson (11)

    Houston, Texas, 77030-4009

  • Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(4)

    San Antonio, Texas, 78229

  • Mayo Clinic - Arizona Cancer Clinical Research Unit

    Scottsdale, Arizona, 85259

Other trials in United States

United Kingdom4 sites

  • Novartis Investigative Site

    Bradford, BD9 6RJ

  • Novartis Investigative Site

    London, EC1A 7BE

  • Novartis Investigative Site

    London, SE1 9RT

  • Novartis Investigative Site

    Manchester, M20 4BX

Other trials in United Kingdom

About this study

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.
Read the detailed description

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

Being tested
BHQ880, Zoledronic acid
Keywords
Multiple myeloma, bone disease, antibody
Medical subject headings
Multiple Myeloma, Bone Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00741377
Study groupRoleWhat they receive
BHQ880 + zoledronic acidExperimentalBHQ880 3-40 mg/kg in combination with zoledronic acid 4 mg on day 1 of a 28-day cycle.
Receives: Drug: BHQ880; Drug: Zoledronic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy

Secondary outcomes (5)

  1. Characterize acute and chronic safety and tolerability of BHQ880

    Measured: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy

  2. Characterize single-dose and repeated-dose pharmacokinetic profiles of BHQ880

    Measured: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy

  3. Assess the potential immunogenicity of BHQ880

    Measured: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy

  4. Characterize the binding kinetics of DKK1/BHQ880 complex (free and BHQ880 bound DKK1) in serum

    Measured: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy

  5. Determine the pharmacodynamic effects of BHQ880 by measuring biochemical markers of bone formation, resorption, and metabolism in serum and urine

    Measured: 9 months minimum treatment with BHQ880 or placebo in combination with zoledronic acid and std anti-myeloma therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2008 (estimated)
  2. Study startJan 2009
  3. Primary completionDec 2011
  4. Study completionDec 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00741377
Sponsor's protocol ID
CBHQ880A2102
Other IDs
2008-000411-15, 2008
Status last verified
Feb 2013
First submitted
22 Aug 2008
Last updated
18 Feb 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BHQ880 and Zoledronic acid in people with Multiple Myeloma Bone Disease, run by Novartis Pharmaceuticals at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00741377.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2013.

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