Romosozumab for Osteoporosis in Multiple Myeloma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests romosozumab, a medication for bone health, to determine its safety and effectiveness for individuals with osteoporosis and bone problems related to multiple myeloma, a type of cancer. Researchers aim to assess whether this treatment can enhance bone strength and prevent bone deterioration. It is particularly suitable for postmenopausal women with multiple myeloma who have bone issues, such as fractures or weak bones, and have not recently used certain bone treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that romosozumab is likely to be safe for humans?

Research has shown that romosozumab is generally well-tolerated. In a large study, only 5.2% of patients experienced mild reactions at the injection site. Other studies have found that romosozumab significantly increases bone strength, which is crucial for treating weak bones due to osteoporosis and bone disease related to myeloma.

The FDA has approved romosozumab for treating osteoporosis in postmenopausal women, indicating it has passed safety checks for similar conditions. Overall, evidence suggests that romosozumab is a safe option, but potential side effects should be discussed with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Romosozumab is unique because it targets a protein called sclerostin, which is involved in bone formation. Unlike standard osteoporosis treatments such as bisphosphonates and denosumab, which primarily work by slowing down bone loss, romosozumab encourages new bone growth while also decreasing bone breakdown. This dual-action approach not only strengthens bones but also has the potential to be more effective in improving bone density, making it particularly promising for patients with osteoporosis in multiple myeloma. Researchers are excited because this mechanism offers a fresh avenue to tackle bone weakness, a common issue in multiple myeloma patients.

What evidence suggests that romosozumab might be an effective treatment for osteoporosis in multiple myeloma?

Research shows that romosozumab, the treatment under study in this trial, can significantly improve bone strength. Studies have found that after 12 months, bone density increased by 13.3% in the spine and 6.9% in the hip. Additionally, participants taking romosozumab had a 73% lower chance of new spinal fractures. In postmenopausal women with multiple myeloma and osteoporosis, romosozumab may help build new bone and reduce bone loss. These findings suggest that romosozumab could effectively improve bone health in those with osteoporosis and bone issues related to multiple myeloma. ^{6 7 8 9 10}

Who Is on the Research Team?

Carlyn R Tan, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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, 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]

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]

Citations

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Bone health in cancer: perspective on the use of ... Regarding its safety profile, romosozumab demonstrated a higher incidence of serious cardiovascular events in one head-to-head randomized trial ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5402913/

Profile of romosozumab and its potential in the ... Consistent with the findings in Phase I and Phase II studies, there were significant gains in BMD by 12 months in the lumbar spine (13.3%), total hip (6.9%), ...

3. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04563-z

Romosozumab in osteoporosis: yesterday, today and tomorrow The results showed that at month 12, patients who received romosozumab had a 73% lower risk of new vertebral fracture and a 36% lower risk of ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02848

Romosozumab for the Management of Myeloma-related ... Giving romosozumab may increase bone formation and decrease resorption in postmenopausal women with multiple myeloma and osteoporosis. Eligibility Criteria ...

5. withpower.com withpower.com/trial/romosozumab-for-osteoporosis-in-multiple-myeloma-fcebf

Romosozumab for Osteoporosis in Multiple Myeloma Romosozumab significantly reduces the incidence of new vertebral fractures in postmenopausal women with osteoporosis after just 12 months of treatment, showing ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12452266/

Romosozumab in postmenopausal women with smoldering ... In this study, we provide novel evidence that ROMO may improve bone health in patients with MM, without adversely affecting the underlying disease. Osteoporosis ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7996128/

Early clinical effects, safety, and predictors of the ... Percent changes from baseline in the spine and total hip BMD after 12 months of romosozumab treatment were 10.67% and 2.04%, respectively.

8. academic.oup.com academic.oup.com/jbmrplus/advance-article-pdf/doi/10.1093/jbmrpl/ziaf144/64167235/ziaf144.pdf

a prospective 12-mo study - Oxford Academic In this study, 8 women with both myeloma and osteoporosis were treated with romosozumab (ROMO), a therapy that helps to build bone and reduce ...

9. asbmr.onlinelibrary.wiley.com asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbm4.10518

The role of bone‐modifying agents in myeloma bone disease Romosozumab is generally well tolerated. In the large phase III FRAME trial, injection site reactions were seen in 5.2% of patients in the ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/761062Orig1s000MultidisciplineR.pdf

761062Orig1s000 - accessdata.fda.gov Romosozumab also significantly increased bone mineral density (BMD) at all sites. At month 12, compared with placebo, romosozumab increased ...