Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants (Z-MARK)

May 3, 2021 updated by: Novartis Pharmaceuticals

Bone Marker-directed Dosing of ZOMETA® (Zoledronic Acid) for the Prevention of Skeletal Complications in Patients With Advanced Multiple Myeloma.

This study evaluated the effectiveness and safety of a dosing method for zoledronic acid in preventing skeletal complications in multiple myeloma participants who have been on an intravenous (IV) bisphosphonate for about one to two years.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

121

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Casa Grande, Arizona, United States, 85222
        • TriValley Cancer Research and Treatment Center
    • California
      • La Verne, California, United States, 91750
        • Wilshire Oncology Medical Group
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center Outpatient Cancer Ctr. (4)
      • Mountain View, California, United States, 94040
        • Palo Alto Medical Foundation Hematology/Oncology
      • San Gabriel, California, United States, 91776
        • Oncology Care Medical Associates
      • San Jose, California, United States, 95128
        • Santa Clara Valley Health & Hospital System
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado U of Colorado Cancer Center
    • Connecticut
      • Stamford, Connecticut, United States, 06902
        • Hematology Oncology PC
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Washington Hospital Center
    • Florida
      • Boynton Beach, Florida, United States, 33435
        • Palm Beach Institute of Hematology Oncology
      • Miami Shores, Florida, United States, 33138
        • Innovative Medical Research of South Florida Innovative Med Research
      • Ocoee, Florida, United States, *see dep*
        • Cancer Centers of Florida PA Cancer Centers of Central FL
      • Orange Park, Florida, United States, 32073
        • Integrated Community Oncology Network Florida Oncology Associates
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center /Cardinal Bernardin Cancer Loyola Univ Med Ctr
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Greenebaum Cancer Center
      • Bethesda, Maryland, United States, 20817
        • Center for Cancer & Blood Disorders
      • Clinton, Maryland, United States, 20735
        • Oncology - Hematology Associates, PA Oncology Hematology Assoc
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute Clinical Research Coordinator
      • Boston, Massachusetts, United States, 02131
        • Boston VA Healthcare Boston VA
      • Pittsfield, Massachusetts, United States, 01201-8298
        • Berkshire Hematology Oncology
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • N MS Hematology & Oncology
    • Nebraska
      • Omaha, Nebraska, United States, 68122-1799
        • Hematology & Oncology Consultants, PC Hematology & Oncology
    • New Jersey
      • Somerset, New Jersey, United States, 08873
        • Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)
      • Voorhees, New Jersey, United States, 08043
        • Cooper Cancer Center
    • New York
      • Rochester, New York, United States, 14621
        • Rochester General Hospital / Lipson Cancer Center Lipson Cancer Center
      • Rochester, New York, United States, 14642
        • University of Rochester MC / James P. Wilmot Cancer Center James P. Wilmot Cancer Center
      • Syracuse, New York, United States, 13210
        • SUNY - Upstate Medical University Div. of Hematology-Oncology
    • North Carolina
      • Hickory, North Carolina, United States, 28602
        • Carolina Oncology Specialists, PC
    • Pennsylvania
      • Langhorne, Pennsylvania, United States, 19047
        • Regional Hematology-Oncology Associates PC
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Temple University
    • South Carolina
      • Charleston, South Carolina, United States, 29403
        • Medical Associates, PA
      • Mount Pleasant, South Carolina, United States, 29464
        • Low Country Hematology Oncology Dept of Lowcountry Hem/Onc
      • West Columbia, South Carolina, United States, 29169
        • Lexington Oncology Associates
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Research Institute
    • Texas
      • Tyler, Texas, United States, 75701
        • East Texas Medical Center Cancer Institute
      • Tyler, Texas, United States, 75701
        • Blood and cancer Center of East Texas
    • Utah
      • Ogden, Utah, United States, 84403-3105
        • Northern Utah Cancer Associates Dept.ofNorthernUtahAssoc.
      • Provo, Utah, United States, 84604
        • Central Utah Clinic Central Utah Clinic (8)
    • Virginia
      • Newport News, Virginia, United States, 23601
        • Peninsula Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Health Research Center Clinical Trial Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Confirmed diagnosis of multiple myeloma
  • Have been on zoledronic acid or pamidronate for 1-2 years and therapy must have been initiated for osteolytic lesion, bone fracture, spinal compression, or osteopenia due to multiple myeloma
  • Stable renal function

Exclusion Criteria:

  • Known sensitivity to bisphosphonates
  • Receiving investigational drugs considered not safe for co-administration or have a significant effect on bone turnover
  • Current active dental problems
  • Had bone marrow transplant or blood stem cell transplant within 2 months before study entry or planned transplant within 2 months following enrollment

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zoledronic acid
Participants received 4 milligrams (mg) or a reduced dose, i.e., 3.5 mg, or 3.3 mg or 3.0 mg of Zoledronic acid as an IV infusion over a minimum of 15 minutes, every 4 weeks or every 12 weeks for up to 96 weeks based on the participants most recent urine N-telopeptide of type 1 collagen (NTx) measurement (greater than or equal to [≥] 50 nanomoles per millimoles [nmol/mmol] creatinine or <50 nmol/mmol creatinine, respectively).
Drug: zoledronic acid
Zoledronic acid concentrate (4 mg/5 milliliters [ml]) was diluted in 100 mL sterile 0.9% calcium-free sodium chloride or 5% dextrose injection, administered IV, either 4 or 12 weeks for 96 weeks.
Other Names:
  • Zometa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With ≥1 SRE at the End of 1 Year on Study
Time Frame: 1 year
SRE was defined as pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or hypercalcemia of malignancy (HCM). SRE was assessed by centrally read radiographic bone surveys.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to First SRE on Study
Time Frame: Up to 2 years
The time to first SRE is defined as the date of enrollment to the date of the first occurrence of any SRE on the study. SRE includes pathological fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM. Participants who drop-out was treated as censored observations. Time to first SRE on the study was assessed by the Kaplan-Meier method.
Up to 2 years
Percentage of Participants Who Experienced Pathologic Bone Fracture
Time Frame: Years 1 and 2
Pathologic bone fractures are defined as bone fractures that occur spontaneously or as a result of trivial trauma.
Years 1 and 2
Percentage of Participants Who Experienced Spinal Cord Compression
Time Frame: Years 1 and 2
Spinal cord compression is caused by the impingement of a tumor on the spinal cord and is associated with neurologic impairment and/or back pain.
Years 1 and 2
Percentage of Participants Who Experienced Radiation to Bone
Time Frame: Years 1 and 2
Radiation therapy to bone events includes irradiation of bone to palliate painful lesions, to treat or prevent pathologic fractures, or to treat or prevent spinal cord compression.
Years 1 and 2
Percentage of Participants Who Experienced Surgery to Bone
Time Frame: Years 1 and 2
Surgery to bone events includes surgical procedures that are performed to set or stabilize pathologic fractures or areas of spinal cord compression and surgical procedures that are performed to prevent an imminent pathologic fracture or spinal cord compression.
Years 1 and 2
Percentage of Participants Who Experienced HCM
Time Frame: Years 1 and 2
HCM is defined as corrected serum calcium ≥ 12.0 milligrams per deciliter (mg/dL) (3.00 millimoles per liter [mmol/L]), or a lower level of hypercalcemia that was symptomatic and required active treatment other than rehydration.
Years 1 and 2
Skeletal Related Event (SRE) Rate
Time Frame: Years 1 and 2
The SRE rate for each participant was calculated as the number of SREs/total follow-up time. SRE included pathological bone fracture, initiation of radiotherapy or surgery on bone, spinal cord compression, or HCM.
Years 1 and 2
Change From Baseline in Urinary N-telopeptide of Type 1 Collagen (uNTx)
Time Frame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84 and 100/End of Study (EOS)
uNTx is a biomarker used to measure the rate of bone turnover found in urine.
Baseline and Weeks 12, 24, 36, 48, 60, 72, 84 and 100/End of Study (EOS)
Time to Death
Time Frame: Up to 2 years
Time to death was defined as the time from the date of enrollment to the date of death. Participants who dropped out or completed the study were considered censored observations. Time to death was assessed by Kaplan-Meier method.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 7, 2007

Primary Completion (Actual)

April 3, 2012

Study Completion (Actual)

April 3, 2012

Study Registration Dates

First Submitted

February 14, 2008

First Submitted That Met QC Criteria

February 22, 2008

First Posted (Estimate)

February 25, 2008

Study Record Updates

Last Update Posted (Actual)

May 26, 2021

Last Update Submitted That Met QC Criteria

May 3, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CZOL446EUS129

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Myeloma

Clinical Trials on zoledronic acid

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Montenegro

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe