Clinical trial NCT02286830: Prolonged Protection From Bone Disease in Multiple Myeloma
Official title: Magnolia Study Prolonged Protection From Bone Disease in Multiple Myeloma. An Open Label Phase 3 Multicenter International Randomised Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Myeloma
Keywords: osteolysis
zoledronic acid
osteonecrosis
bone markers
low-dose CT
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2014-11-10
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: time to first skeletal related event after randomisations at year two
timeFrame: From year two to year four
Secondary outcomes:
measure: 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.
timeFrame: 4 years
Other outcomes:
measure: Number of lesions identified with conventional radiography and low-dose CT
timeFrame: 4 years
measure: register incidence of osteonecrosis of the jaw
timeFrame: 4 years
measure: register creatinine levels in serum
timeFrame: 4 years
measure: register ionized calcium in serum
timeFrame: 4 years
Locations:
city: Odense C
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Department of hematology, Odense University Hospital, Denmark
name: Thomas LunD, MD Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: