Prolonged Protection From Bone Disease in Multiple Myeloma (Magnolia)

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

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

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

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.

After two years of zoledronic acid treatment patients will be randomized to A continue treatment B stop treatment.

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.

Patients will have low-dose CT and conventional x-ray made at predefined time points to compare the sensitivity between the two modalities

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