Prolonged Protection From Bone Disease in Multiple Myeloma

Study Overview
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Brief Summary
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Main hypothesis: Patients who continue zoledronic acid after year 2 have longer time until progression in bone disease compared to patients who stop treatment after two years? Secondary hypothesis: Serum will bone markers increase prior to progression in bone disease in the individual patient? Secondary hypothesis: Low-dose CT will detect more cases of osteolytic bone disease in Multiple Myeloma compared to conventional radiography

Detailed Description
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Newly diagnosed myeloma patients will be followed for 4 years. The first two years they will be treated with zoledronic acid monthly. At year 2 they will be randomized to A continue treatment for 2 more years or B stop treatment. The primary outcome of the study will be time to progressive bone disease from year 2 and onward. Serum bone markers will be measured throughout the study. In patients who experience progressive bone disease, development of bone markers prior to the radiological progression will be investigated to see the if it could have been predicted with the use of serum markers During the four year period patients will have low-dose CT superior and conventional radiography made at predefined time points. The secondary outcome of the study is to compare the sensitivity of the two modalities

Official Title
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Magnolia Study Prolonged Protection From Bone Disease in Multiple Myeloma. An Open Label Phase 3 Multicenter International Randomised Trial

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: Symptomatic Multiple Myeloma regardless of bone disease status Signed Informed Consent Age ≥ 18 years Remaining life expectancy ≥ 2 years Any concurrently anti-myeloma treatment are allowed Exclusion Criteria: Previous treatment with bisphosphonate within the last 6 months Severely reduced renal function (creatinine clearance <30 mL/min despite fluid replacement) Known concurrent malignancy, excluding skin cancer Known hypersensitivity to zoledronic acid Pregnant or lactating women Women of childbearing potential or men engaging in sexual activity with a woman of childbearing potential who refuse to use contraception

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 |
| --- | --- |
| Active Comparator: zoledronic acid<br>treatment with zoledronic acid for 4 years | Drug: Zoledronic acid<br>* Zoledronic acid will be given to all participants for two years. Then patients will be randomized to A receive 2 more years of treatment or B stop treatment.<br>* Other names: Zometa;|
| Placebo Comparator: no treatment<br>treatment with zoledronic acid withheld after two years | Drug: Zoledronic acid<br>* Zoledronic acid will be given to all participants for two years. Then patients will be randomized to A receive 2 more years of treatment or B stop treatment.<br>* Other names: Zometa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to first skeletal related event after randomisations at year two | After two years of zoledronic acid treatment patients will be randomized to A continue treatment B stop treatment. | From year two to year four | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Value of serum bone marker ratio (bone resorption / bone formation markers) as predictor of skeletal related related events analysed by time-dependent multiparameter Cox regression analysis. | Development in bone markers prior to progression in osteolytic lesions will be investigated | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteolysis, zoledronic acid, osteonecrosis, bone markers, low-dose CT