A Multiple Myeloma Trial in Patients With Bone Metastases

Study Overview
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Brief Summary
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The purpose of this trial is to study the safety of treating patients with multiple myeloma and at least one bone lesion with zoledronic acid 4mg intravenously (IV) every 3 - 4 weeks for 2 years. Patients will receive a zoledronic acid infusion for 15 minutes or 30 minutes.

Official Title
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A Multicenter,Open Label, Randomized Trial Evaluating the Duration of Infusion of Zoledronic Acid 4 mg IV in Multiple Myeloma Patients With Bone Metastases

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: Patients 18 years of age or older Confirmed diagnosis of Multiple Myeloma Stable renal function defined as two serum creatinine determinations of < 3 mg/dL Calculated creatinine clearance of greater than or equal to 30 mL/min ECOG Performance Status of 0 or 1 Life expectancy of greater than or equal to 9 months If the patient is of child-bearing potential, a negative pregnancy test is required at screening, while postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Ability to comply with trial requirements and give informed consent. Exclusion Criteria: IV Bisphosphonate therapy for more than 3 years. Patients with a diagnosis of amyloidosis. Known hypersensitivity to zoledronic acid or other bisphosphonates Pregnant patients or lactating patients. Women of childbearing potential not on a medically recognized form of contraception Patients with uncontrolled cardiovascular disease, hypertension, and Type 2 diabetes mellitus.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15 Minute Infusion<br>Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 15-minute infusion time, but increasing to a 30-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12 weeks | Drug: zoledronic acid<br>* 4 mg zoledronic acid in 250 mL of calcium-free solution (i.e., 0.9% sodium chloride or 5% glucose) administered intravenously.<br>* Other names: ZOMETA®;|
| Experimental: 30 Minute Infusion<br>Participants received 4 mg zoledronic acid intravenously, in 250 mL of fluid, every 3-4 weeks for up to 24 months, over a 30-minute infusion time, but increasing to a 45-minute infusion time if they experienced a clinically relevant rise in serum creatinine that resolved in less than 12-weeks. | Drug: zoledronic acid<br>* 4 mg zoledronic acid in 250 mL of calcium-free solution (i.e., 0.9% sodium chloride or 5% glucose) administered intravenously.<br>* Other names: ZOMETA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With a Significant Increase in Serum Creatinine at 12 Months | The primary renal safety endpoint was the number of participants with a clinically relevant increase in serum creatinine at 12 months. Serum creatinine was determined prior to each zoledronic acid infusion for all Participants and was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value. | Baseline and 12 Months | 
| The Number of Participants With Disease Progression |  | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With a Significant Increase in Serum Creatinine at 24 Months | Serum Creatinine was considered to be significantly increased if there was an increase of 0.5 mg/dL or more or a doubling of the baseline serum creatinine value. | Baseline and 24 Months | 
| Time to First Significant Increase in Serum Creatinine | Median time to event in participants who had a clinically relevant increase in serum creatinine. | Up to 24 months | 
| Zoledronic Acid Concentrations | Samples for drug concentration analysis were drawn at 10 and 15 minutes into the infusion for participants in the 15-minute infusion group and at 25 and 30 minutes into the infusion for patients in the 30-minute infusion group. The mean and median zoledronic acid concentrations were greater in the 15-minute group than in the 30-minute group at both sampling timepoints. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Z-MAX, multiple myeloma, zoledronic acid, bone metastases