Clinical trial NCT05775094: A Study of Romosozumab in Women With Multiple Myeloma and Osteoporosis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Osteoporosis
Multiple Myeloma
Keywords: Romosozumab
23-038
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2023-03-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, single-arm.
Primary purpose: TREATMENT

Brief 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 \< 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).

Primary outcomes:
measure: Percent change in bone formation marker, P1NP
timeFrame: up to 2 years
Secondary outcomes:
measure: Incidence and severity of adverse events
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Limited Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Limited Protocol Activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Carlyn Tan, MD
role: PRINCIPAL_INVESTIGATOR
References: