a study of romosozumab in women with multiple myeloma and osteoporosis

Conditions: Osteoporosis; Multiple Myeloma

Summary: 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).


Eligibility criteria:
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: 1. 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) 2. renal insufficiency: creatinine clearance \ 2 mg/dl) 3. anemia: hemoglobin \> 2 g/dl below the lower limit of normal, or a hemoglobin value \<10 g/dl 4. 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 (\ 10.5 mg/dl).

Keywords: romosozumab 23-038