Multiple MyelomaPhase 4Z-MARKNCT00622505

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

A Phase 4 study testing zoledronic acid in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 42 sites in United States.

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 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Multiple Myeloma
What is being tested?: zoledronic acid
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 121 participants
Where: 42 sitesUnited States
Study dates: 7 Nov 2007to 3 Apr 2012
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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.

Trial locations and contacts

42 sites in 1 country.

City, postcode or hospital

42 sites in 1 country

United States42 sites

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

Other trials in United States

About this study

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

Conditions: Multiple Myeloma
Being tested: zoledronic acid
Keywords: Multiple myeloma, zoledronic acid, skeletal complications, bone
Medical subject headings: Multiple Myeloma

What participants receive

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

zoledronic acidDrug
Also called Zometa
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.

Study groups in NCT00622505
Study group	Role	What they receive
Zoledronic acid	Experimental	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). Receives: Drug: zoledronic acid

What is being measured

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

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.
Measured: 1 year

Secondary outcomes (9)

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.
Measured: Up to 2 years
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.
Measured: Years 1 and 2
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.
Measured: Years 1 and 2
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.
Measured: Years 1 and 2
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.
Measured: Years 1 and 2
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.
Measured: Years 1 and 2
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.
Measured: Years 1 and 2
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.
Measured: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84 and 100/End of Study (EOS)
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.
Measured: Up to 2 years

Timeline

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

7 Nov 20073 Apr 2012

First posted25 Feb 2008 (estimated)
Study start7 Nov 2007
Primary completion3 Apr 2012
Study completion3 Apr 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Multiple MyelomaStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 4
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 121 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00622505
Sponsor's protocol ID: CZOL446EUS129
Acronym: Z-MARK
Status last verified: May 2021
First submitted: 14 Feb 2008
Last updated: 26 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 26644410

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 26 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Bone Marker-directed Dosing of ZOMETA® (Zoledronic Acid) for the Prevention of Skeletal Complications in Patients With Advanced Multiple Myeloma.
ClinicalTrials.gov ID: NCT00622505
Acronym / sponsor ID: Z-MARK / CZOL446EUS129
Conditions: Multiple Myeloma
Keywords: Multiple myeloma, zoledronic acid, skeletal complications, bone
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 121 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 7 Nov 2007 (actual)
Primary completion: 3 Apr 2012 (actual)
Study completion: 3 Apr 2012 (actual)
First posted: 25 Feb 2008 (estimated)
Results: Posted 26 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Zoledronic acid	Experimental	Drug: zoledronic acidParticipants 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).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
zoledronic acidAlso: ZometaZoledronic 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.	Drug	Zoledronic acid

Primary outcome

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.

9 secondary outcomes

Time to First SRE on Study
Time frame: Up to 2 years
Percentage of Participants Who Experienced Pathologic Bone Fracture
Time frame: Years 1 and 2
Percentage of Participants Who Experienced Spinal Cord Compression
Time frame: Years 1 and 2
Percentage of Participants Who Experienced Radiation to Bone
Time frame: Years 1 and 2
Percentage of Participants Who Experienced Surgery to Bone
Time frame: Years 1 and 2
Percentage of Participants Who Experienced HCM
Time frame: Years 1 and 2
Skeletal Related Event (SRE) Rate
Time frame: 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)
Time to Death
Time frame: Up to 2 years

Results and safety

Results posted to the registry on 26 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Zoledronic Acid Every 12 Weeks	79	50
Zoledronic Acid Every 4 Weeks or 12 Weeks	42	19

Primary outcome: Percentage of Participants With ≥1 SRE at the End of 1 Year on Study

Time frame: 1 year. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Zoledronic Acid Every 12 Weeks n = 79	Zoledronic Acid Every 4 Weeks or 12 Weeks n = 42
Value	0 (NA to NA)	0.17 (0.05 to 0.28)

Population analysed: ITT analysis set included all participants who were enrolled in this study.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 2 Years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Zoledronic Acid Every 12 Weeks	23 of 79 (29.1%)	70 of 79 (88.6%)	2 of 79
Zoledronic Acid Every 4 Weeks or 12 Weeks	25 of 42 (59.5%)	41 of 42 (97.6%)	2 of 42

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 26644410Raje 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.

Related trials for Multiple Myeloma

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
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Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
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Active, not recruitingPhase 1/2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

42 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing zoledronic acid in people with Multiple Myeloma, run by Novartis Pharmaceuticals at 42 sites in United States.

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 3 inclusion and 5 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 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With ≥1 SRE at the End of 1 Year on Study (time frame: 1 year). 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 NCT00622505, which also lists 1 linked publication.

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 26 May 2021.