Romosozumab for Osteoporosis in Multiple Myeloma

Recruiting at 7 trial locations

Overseen By Heiko Schoder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: PTH analogs, Antiresorptives

Disqualifiers: Male, Cardiovascular event, Osteonecrosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing romosozumab, a medication that helps build and strengthen bones, in postmenopausal people with multiple myeloma. These patients often have weak bones due to osteoporosis and bone disease related to their condition. Romosozumab works by promoting new bone growth and preventing bone loss. Romosozumab is a recently approved monoclonal antibody that promotes bone formation and prevents bone resorption.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot be on concurrent antiresorptive therapy (medications that slow down bone loss). If you are taking such medications, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug Romosozumab for osteoporosis in multiple myeloma?

Research shows that Romosozumab is effective in treating osteoporosis, as it helps strengthen bones and reduce the risk of fractures. This is based on studies involving patients with osteoporosis, where Romosozumab was shown to be beneficial, suggesting it might also help those with osteoporosis due to multiple myeloma. ^{1 2 3 4 5}

Is Romosozumab safe for humans?

Romosozumab has been studied for osteoporosis and is generally considered safe, with adverse events similar to those in control groups. However, there may be potential cardiovascular risks, so it's important to discuss these with your doctor. ^{2 3 6 7 8}

How is the drug romosozumab unique for treating osteoporosis in multiple myeloma?

Romosozumab is unique because it is a sclerostin inhibitor that both builds new bone and reduces bone breakdown, which is different from many other osteoporosis treatments that only focus on one of these actions. It is administered as a monthly injection, making it convenient compared to some treatments that require more frequent dosing. ^{3 9 10 11 12}

Research Team

Carlyn R Tan, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for postmenopausal women with multiple myeloma and osteoporosis. Participants must be over 18, able to follow study procedures, have documented MM, and show signs of bone weakness or fractures. They can't join if they've had certain treatments recently, have low vitamin D (unless corrected), abnormal calcium levels, a history of jawbone problems or recent serious heart events.

Inclusion Criteria

I have not had a menstrual cycle in the last 12 months.

I last took oral bisphosphonates more than 3 months ago.

My tests show a high number of plasma cells in my bone marrow or a confirmed plasmacytoma.

Exclusion Criteria

I have had dental or oral surgery that hasn't fully healed.

My vitamin D levels are currently below 20 ng/mL.

I have had a heart attack or stroke in the last year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Romosozumab is administered at 210 mg SC once monthly for 12 months in conjunction with antimyeloma therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of adverse events

up to 12 months

Treatment Details

Interventions

• Romosozumab

Trial Overview The study tests Romosozumab's effects on bone formation and breakdown in women with both multiple myeloma and osteoporosis. It aims to determine the safety and effectiveness of this treatment for managing myeloma-related bone disease.

Participant Groups

Group I: Romosozumab Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Romosozumab significantly reduces the incidence of new vertebral fractures in postmenopausal women with osteoporosis after just 12 months of treatment, showing strong efficacy compared to both placebo and active bisphosphonate controls.

However, there is a concerning numerical increase in cardiovascular events associated with romosozumab, suggesting it should be used cautiously, especially in patients with a history of cardiovascular issues or high cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. Fixen, C., Tunoa, J.[2021]

Romosozumab significantly increases bone mineral density (BMD) in patients with osteoporosis, showing greater gains at the lumbar spine and hip compared to teriparatide after 12 months, making it an effective treatment option.

While romosozumab reduces fracture risk in high-risk postmenopausal women, it is associated with a higher incidence of serious cardiovascular events, so it should be avoided in patients with recent history of myocardial infarction or stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis. Nealy, KL., Harris, KB.[2021]

In a study of 130 postmenopausal osteoporosis patients, those who were treatment-naïve showed the greatest increase in lumbar spine bone mineral density (BMD) after six months of romosozumab treatment, with a 13.6% increase compared to lower increases in patients previously treated with bisphosphonates, denosumab, or teriparatide.

The early changes in bone turnover markers, specifically PINP and TRACP-5b, were significant predictors of the increase in lumbar spine BMD, indicating that monitoring these markers could help assess treatment response to romosozumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. Ebina, K., Hirao, M., Tsuboi, H., et al.[2021]

In a study of 148 postmenopausal osteoporosis patients, those who were treatment-naïve showed the greatest increase in bone mineral density (BMD) after 12 months of romosozumab treatment, with an 18.2% increase in lumbar spine BMD compared to lower increases in patients previously treated with bisphosphonates or other therapies.

The effectiveness of romosozumab in increasing BMD was significantly influenced by the type of prior treatment and early changes in bone turnover markers, indicating that these factors can help predict treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. Ebina, K., Tsuboi, H., Nagayama, Y., et al.[2021]

Romosozumab, a new treatment for osteoporosis, has been associated with several significant adverse events, including injection site pain, cardiac failure, renal impairment, pneumonia, and increased blood alkaline phosphatase levels, based on an analysis of 1,948 reported adverse events from the FDA Adverse Event Reporting System.

The study highlights the importance of monitoring these potential adverse reactions in clinical settings, as the reporting odds ratios indicate a strong association between romosozumab and these adverse events, suggesting that healthcare providers should be cautious when prescribing this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pharmacovigilance analysis of FDA adverse event reporting system events for romosozumab. Chen, Z., Li, M., Li, S., et al.[2023]

Romosozumab significantly reduces the risk of fractures in postmenopausal women with osteoporosis, showing a 63% lower risk of new vertebral fractures and a 41% lower risk of hip fractures compared to other therapies, based on data from six randomized controlled trials involving over 5,600 participants.

The treatment also leads to substantial increases in bone mineral density (BMD) at key sites like the lumbar spine and hip, while demonstrating a good safety profile with no significant increase in adverse events compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. Liu, Y., Cao, Y., Zhang, S., et al.[2019]

Romosozumab significantly increases spine bone mineral density (BMD) after 12 months of treatment, with a 10.67% increase observed in a study of 262 patients, indicating its efficacy in treating spine osteoporosis.

The treatment was associated with a low incidence of new fractures (only five cases) and no fatal adverse events, highlighting its safety profile, especially in patients not previously treated with other osteoporosis medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early clinical effects, safety, and predictors of the effects of romosozumab treatment in osteoporosis patients: one-year study. Tominaga, A., Wada, K., Okazaki, K., et al.[2022]

Romosozumab significantly increased bone mineral density (BMD) in postmenopausal women with low BMD over 24 months, with the highest gains observed in those receiving the 210 mg monthly dose (15.1% increase in lumbar spine and 5.4% in total hip).

Transitioning from romosozumab to denosumab continued to enhance BMD, while discontinuation of romosozumab led to a decrease in BMD back toward pretreatment levels, indicating that the effects of romosozumab are reversible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. McClung, MR., Brown, JP., Diez-Perez, A., et al.[2019]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Effectiveness of romosozumab in patients with osteoporosis at high fracture risk: a Japanese real-world study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Romosozumab: A Novel Injectable Sclerostin Inhibitor With Anabolic and Antiresorptive Effects for Osteoporosis. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

A pharmacovigilance analysis of FDA adverse event reporting system events for romosozumab. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Romosozumab treatment in postmenopausal women with osteoporosis: a meta-analysis of randomized controlled trials. [2019]

8. England pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Early clinical effects, safety, and predictors of the effects of romosozumab treatment in osteoporosis patients: one-year study. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Real-world effects and adverse events of romosozumab in Japanese osteoporotic patients: A prospective cohort study. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Romosozumab Among Postmenopausal Women With Osteoporosis and Mild-to-Moderate Chronic Kidney Disease. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. [2019]