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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
zoledronic acid
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Multiple Myeloma focused on measuring Multiple myeloma, zoledronic acid, skeletal complications, bone

Eligibility Criteria

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

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.

Sites / Locations

  • TriValley Cancer Research and Treatment Center
  • Wilshire Oncology Medical Group
  • Cedars Sinai Medical Center Outpatient Cancer Ctr. (4)
  • Palo Alto Medical Foundation Hematology/Oncology
  • Oncology Care Medical Associates
  • Santa Clara Valley Health & Hospital System
  • University of Colorado U of Colorado Cancer Center
  • Hematology Oncology PC
  • Washington Hospital Center
  • Palm Beach Institute of Hematology Oncology
  • Innovative Medical Research of South Florida Innovative Med Research
  • Cancer Centers of Florida PA Cancer Centers of Central FL
  • Integrated Community Oncology Network Florida Oncology Associates
  • Cleveland Clinic Florida
  • Loyola University Medical Center /Cardinal Bernardin Cancer Loyola Univ Med Ctr
  • University of Maryland Greenebaum Cancer Center
  • Center for Cancer & Blood Disorders
  • Oncology - Hematology Associates, PA Oncology Hematology Assoc
  • Dana Farber Cancer Institute Clinical Research Coordinator
  • Boston VA Healthcare Boston VA
  • Berkshire Hematology Oncology
  • N MS Hematology & Oncology
  • Hematology & Oncology Consultants, PC Hematology & Oncology
  • Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)
  • Cooper Cancer Center
  • Rochester General Hospital / Lipson Cancer Center Lipson Cancer Center
  • University of Rochester MC / James P. Wilmot Cancer Center James P. Wilmot Cancer Center
  • SUNY - Upstate Medical University Div. of Hematology-Oncology
  • Carolina Oncology Specialists, PC
  • Regional Hematology-Oncology Associates PC
  • Temple University Temple University
  • Medical Associates, PA
  • Low Country Hematology Oncology Dept of Lowcountry Hem/Onc
  • Lexington Oncology Associates
  • Avera Research Institute
  • Blood and Cancer Center of East Texas
  • East Texas Medical Center Cancer Institute
  • Northern Utah Cancer Associates Dept.ofNorthernUtahAssoc.
  • Central Utah Clinic Central Utah Clinic (8)
  • Peninsula Cancer Institute
  • Swedish Cancer Institute
  • West Virginia University Health Research Center Clinical Trial Research Unit

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zoledronic acid

Arm Description

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).

Outcomes

Primary Outcome Measures

Percentage of Participants With ≥1 SRE at the End of 1 Year on Study
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.

Secondary Outcome Measures

Time to First SRE on Study
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.
Percentage of Participants Who Experienced Pathologic Bone Fracture
Pathologic bone fractures are defined as bone fractures that occur spontaneously or as a result of trivial trauma.
Percentage of Participants Who Experienced Spinal Cord Compression
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.
Percentage of Participants Who Experienced Radiation to Bone
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.
Percentage of Participants Who Experienced Surgery to Bone
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.
Percentage of Participants Who Experienced HCM
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.
Skeletal Related Event (SRE) Rate
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.
Change From Baseline in Urinary N-telopeptide of Type 1 Collagen (uNTx)
uNTx is a biomarker used to measure the rate of bone turnover found in urine.
Time to Death
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.

Full Information

First Posted
February 14, 2008
Last Updated
May 3, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00622505
Brief Title
Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
Acronym
Z-MARK
Official Title
Bone Marker-directed Dosing of ZOMETA® (Zoledronic Acid) for the Prevention of Skeletal Complications in Patients With Advanced Multiple Myeloma.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
November 7, 2007 (Actual)
Primary Completion Date
April 3, 2012 (Actual)
Study Completion Date
April 3, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple myeloma, zoledronic acid, skeletal complications, bone

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
121 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zoledronic acid
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Other Intervention Name(s)
Zometa
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With ≥1 SRE at the End of 1 Year on Study
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Time to First SRE on Study
Description
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.
Time Frame
Up to 2 years
Title
Percentage of Participants Who Experienced Pathologic Bone Fracture
Description
Pathologic bone fractures are defined as bone fractures that occur spontaneously or as a result of trivial trauma.
Time Frame
Years 1 and 2
Title
Percentage of Participants Who Experienced Spinal Cord Compression
Description
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.
Time Frame
Years 1 and 2
Title
Percentage of Participants Who Experienced Radiation to Bone
Description
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.
Time Frame
Years 1 and 2
Title
Percentage of Participants Who Experienced Surgery to Bone
Description
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.
Time Frame
Years 1 and 2
Title
Percentage of Participants Who Experienced HCM
Description
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.
Time Frame
Years 1 and 2
Title
Skeletal Related Event (SRE) Rate
Description
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.
Time Frame
Years 1 and 2
Title
Change From Baseline in Urinary N-telopeptide of Type 1 Collagen (uNTx)
Description
uNTx is a biomarker used to measure the rate of bone turnover found in urine.
Time Frame
Baseline and Weeks 12, 24, 36, 48, 60, 72, 84 and 100/End of Study (EOS)
Title
Time to Death
Description
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.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
TriValley Cancer Research and Treatment Center
City
Casa Grande
State/Province
Arizona
ZIP/Postal Code
85222
Country
United States
Facility Name
Wilshire Oncology Medical Group
City
La Verne
State/Province
California
ZIP/Postal Code
91750
Country
United States
Facility Name
Cedars Sinai Medical Center Outpatient Cancer Ctr. (4)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Palo Alto Medical Foundation Hematology/Oncology
City
Mountain View
State/Province
California
ZIP/Postal Code
94040
Country
United States
Facility Name
Oncology Care Medical Associates
City
San Gabriel
State/Province
California
ZIP/Postal Code
91776
Country
United States
Facility Name
Santa Clara Valley Health & Hospital System
City
San Jose
State/Province
California
ZIP/Postal Code
95128
Country
United States
Facility Name
University of Colorado U of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Hematology Oncology PC
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06902
Country
United States
Facility Name
Washington Hospital Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Palm Beach Institute of Hematology Oncology
City
Boynton Beach
State/Province
Florida
ZIP/Postal Code
33435
Country
United States
Facility Name
Innovative Medical Research of South Florida Innovative Med Research
City
Miami Shores
State/Province
Florida
ZIP/Postal Code
33138
Country
United States
Facility Name
Cancer Centers of Florida PA Cancer Centers of Central FL
City
Ocoee
State/Province
Florida
ZIP/Postal Code
*see dep*
Country
United States
Facility Name
Integrated Community Oncology Network Florida Oncology Associates
City
Orange Park
State/Province
Florida
ZIP/Postal Code
32073
Country
United States
Facility Name
Cleveland Clinic Florida
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Loyola University Medical Center /Cardinal Bernardin Cancer Loyola Univ Med Ctr
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
University of Maryland Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Center for Cancer & Blood Disorders
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Oncology - Hematology Associates, PA Oncology Hematology Assoc
City
Clinton
State/Province
Maryland
ZIP/Postal Code
20735
Country
United States
Facility Name
Dana Farber Cancer Institute Clinical Research Coordinator
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston VA Healthcare Boston VA
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02131
Country
United States
Facility Name
Berkshire Hematology Oncology
City
Pittsfield
State/Province
Massachusetts
ZIP/Postal Code
01201-8298
Country
United States
Facility Name
N MS Hematology & Oncology
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
Hematology & Oncology Consultants, PC Hematology & Oncology
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68122-1799
Country
United States
Facility Name
Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)
City
Somerset
State/Province
New Jersey
ZIP/Postal Code
08873
Country
United States
Facility Name
Cooper Cancer Center
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08043
Country
United States
Facility Name
Rochester General Hospital / Lipson Cancer Center Lipson Cancer Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14621
Country
United States
Facility Name
University of Rochester MC / James P. Wilmot Cancer Center James P. Wilmot Cancer Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
SUNY - Upstate Medical University Div. of Hematology-Oncology
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Carolina Oncology Specialists, PC
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28602
Country
United States
Facility Name
Regional Hematology-Oncology Associates PC
City
Langhorne
State/Province
Pennsylvania
ZIP/Postal Code
19047
Country
United States
Facility Name
Temple University Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Medical Associates, PA
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29403
Country
United States
Facility Name
Low Country Hematology Oncology Dept of Lowcountry Hem/Onc
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
Lexington Oncology Associates
City
West Columbia
State/Province
South Carolina
ZIP/Postal Code
29169
Country
United States
Facility Name
Avera Research Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
Blood and Cancer Center of East Texas
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
Facility Name
East Texas Medical Center Cancer Institute
City
Tyler
State/Province
Texas
ZIP/Postal Code
75701
Country
United States
Facility Name
Northern Utah Cancer Associates Dept.ofNorthernUtahAssoc.
City
Ogden
State/Province
Utah
ZIP/Postal Code
84403-3105
Country
United States
Facility Name
Central Utah Clinic Central Utah Clinic (8)
City
Provo
State/Province
Utah
ZIP/Postal Code
84604
Country
United States
Facility Name
Peninsula Cancer Institute
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23601
Country
United States
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
West Virginia University Health Research Center Clinical Trial Research Unit
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26644410
Citation
Raje N, Vescio R, Montgomery CW, Badros A, Munshi N, Orlowski R, Hadala JT, Warsi G, Argonza-Aviles E, Ericson SG, Anderson KC. Bone Marker-Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Results of the Z-MARK Study. Clin Cancer Res. 2016 Mar 15;22(6):1378-84. doi: 10.1158/1078-0432.CCR-15-1864. Epub 2015 Dec 7.
Results Reference
result

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

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