A Study of Romosozumab in Women With Multiple Myeloma and Osteoporosis

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Active, not recruiting; Phase 1

Conditions: Osteoporosis; Multiple Myeloma

Treatments: Drug: Romosozumab

Study type: Interventional

Funder types: Other

Identifiers

NCT05775094

23-038

Details and patient eligibility

About

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).

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 < 40 mL/min or serum creatinine 177µmol/L (>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 (<8.5 or >10.5 mg/dL).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Romosozumab

Experimental group

Description:

Romosozumab will be given on-label for osteoporosis at 210 mg administered SC once monthly for 12 months in conjunction with antimyeloma therapy.

Treatment:

Drug: Romosozumab