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

Study Overview
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Brief Summary
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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.

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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: zoledronic acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zoledronic acid<br>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<br>* 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.<br>* Other names: Zometa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple myeloma, zoledronic acid, skeletal complications, bone