Magnolia: Prolonged Protection From Bone Disease in Multiple Myeloma

Sponsor

Thomas Lund (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02286830

Collaborator

(none)

158

Enrollment

Location

Arms

97.9

Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Zoledronic acid	Phase 4

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

158 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: zoledronic acid treatment with zoledronic acid for 4 years	Drug: Zoledronic acid 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. Other Names: Zometa
Placebo Comparator: no treatment treatment with zoledronic acid withheld after two years	Drug: Zoledronic acid 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. Other Names: Zometa

Arm

Intervention/Treatment

Active Comparator: zoledronic acid

treatment with zoledronic acid for 4 years

Drug: Zoledronic acid

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.

Other Names:

Zometa

Placebo Comparator: no treatment

treatment with zoledronic acid withheld after two years

Drug: Zoledronic acid

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.

Other Names:

Zometa

Outcome Measures

Primary Outcome Measures

time to first skeletal related event after randomisations at year two [From year two to year four]
After two years of zoledronic acid treatment patients will be randomized to A continue treatment B stop treatment.

Secondary Outcome Measures

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. [4 years]
Development in bone markers prior to progression in osteolytic lesions will be investigated

Other Outcome Measures

Number of lesions identified with conventional radiography and low-dose CT [4 years]
Patients will have low-dose CT and conventional x-ray made at predefined time points to compare the sensitivity between the two modalities
register incidence of osteonecrosis of the jaw [4 years]
register creatinine levels in serum [4 years]
nephrotoxicity
register ionized calcium in serum [4 years]
hypocalcemia

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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