A Study of Romosozumab in Women With Multiple Myeloma and Osteoporosis

Study Overview
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Brief Summary
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The purpose of this study is to measure the effect of romosozumab on bone formation and breakdown (resorption) and determine if romosozumab is a safe treatment for osteoporosis and myeloma-related bone disease (MBD) in postmenopausal people with multiple myeloma (MM).

Official Title
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A Pilot Study of Romosozumab Efficacy and Safety for the Management of Myelomarelated OsteoLytic Disease in Postmenopausal Women With Multiple Myeloma and Osteoporosis (REMOLD-MM)

Conditions
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Multiple Myeloma, Osteoporosis

Intervention / Treatment
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* Drug: Romosozumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented MM per International Myeloma Working Group diagnostic criteria (evidence of myeloma defining event attributed to underlying plasma cell disorder): i. Clonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma; and ii. Any one or more of the following myeloma defining events: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder: Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL) Renal insufficiency: creatinine clearance < 40 mL/min or serum creatinine 177µmol/L (>2 mg/dL) Anemia: hemoglobin > 2 g/dL below the lower limit of normal, or a hemoglobin value <10 g/dL Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET/CT Clonal bone marrow plasma cell percentage ≥ 60%; or Involved: uninvolved serum free light chain (FLC) ratio ≥ 100 (involved FLC level be ≥ 10 mg/dL; or >1 focal lesion on MRI studies (at least 5 mm in size) Presence of lytic bone lesion(s) due to MM based on radiographic evidence with at least one measurable lesion (≥0.5 cm in its largest diameter by computerized tomography [CT]) Postmenopausal female, defined as last menstrual cycle at least 12 months prior to study enrollment Must have one of the following: osteoporosis on dual X-ray absorptiometry (DXA) scan; or fragility fracture of the spine or hip; or morphometric spine fracture; or osteopenia with elevated risk of fracture (calculated by the FRAX online calculator) Within 12 months prior to study entry, ≤ 4 doses of prior intravenous (IV) bisphosphonate with the last dose ≥ 3 months prior to study entry. Prior oral bisphosphonates are allowed if the last dose was ≥ 3 months prior to study entry. Prior denosumab use is allowed for the following: For patients who received ≤ 5 consecutive doses of denosumab with the last dose of denosumab received ≥ 3 months prior to study entry. For patients who received ≥ 6 doses of denosumab, IV bisphosphonate should be given at least 1 month after the last dose of denosumab (if the last dose of denosumab was within the past 2 years). Patients are then eligible ≥ 3 months after IV bisphosphonate is received. If ≤ 2 years have elapsed since the last dose of denosumab, IV bisphosphonate is not required, and patients are eligible for the study. Signed informed consent form(s). Individuals with impaired decision-making capacity may enroll if legally authorized representatives consent on behalf of individuals with impaired decision-making capacity. Ability to comply with all study-related procedures in the investigator's judgment 18 years of age or older Exclusion Criteria: Assigned male at birth Received teriparatide or other PTH analog use within 12 months prior to study entry Receiving concurrent antiresorptive therapy History of cardiovascular event (myocardial infarction and/or stroke) within the past 12 months of study entry History of non-healed dental or oral surgery History of osteonecrosis of the jaw 25 (OH) vitamin D levels < 20 ng/mL. Vitamin D repletion will be permitted and subjects may be rescreened once 25 (OH) vitamin D level ≥ 20 ng/mL. Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range per institutional standard (<8.5 or >10.5 mg/dL).

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
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, single-arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Romosozumab<br>Romosozumab will be given on-label for osteoporosis at 210 mg administered SC once monthly for 12 months in conjunction with antimyeloma therapy. | Drug: Romosozumab<br>* Romosozumab will be administered 210 mg SC as two 105 mg prefilled syringes once every 4 weeks x 12 months. No dose adjustments for romosozumab will be permitted. All efforts will be made to administer romosozumab within the defined study visit windows (+/- 14 days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in bone formation marker, P1NP |  | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events | evaluating adverse events using NCI CTCAE v5.0. | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Romosozumab, 23-038