Denosumab for Multiple Myeloma

Overseen By Brea Lipe

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Must be taking: Calcium, Vitamin D

Must not be taking: Bisphosphonates, Corticosteroids

Disqualifiers: Symptomatic MM, Osteonecrosis, Active infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether denosumab, a medication, can safely prevent smoldering multiple myeloma from progressing into full-blown multiple myeloma. Smoldering multiple myeloma is an early form of this blood cancer where patients show no symptoms but remain at risk of developing them. The trial seeks participants diagnosed with smoldering multiple myeloma who have certain risk factors, such as high levels of specific proteins in the blood. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have used certain medications like IV bisphosphonates or high-dose corticosteroids recently. It's best to discuss your current medications with the study team.

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

Research has shown that denosumab has been tested for safety in patients with multiple myeloma, particularly those with serious kidney problems. Results suggest it is safe and effective when measures are taken to prevent low calcium levels in the blood. Other studies compared denosumab to zoledronate and found it more effective at reducing the risk of bone problems. This treatment has been used to prevent bone issues in multiple myeloma patients, demonstrating good results over time. While these studies provide evidence of safety, discussing with healthcare providers what this means for individual situations is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Denosumab is unique because it offers a new approach to treating multiple myeloma by targeting a different pathway compared to traditional therapies. Most treatments for multiple myeloma focus on directly attacking the cancerous plasma cells. However, denosumab works by inhibiting a protein involved in bone resorption called RANKL, which helps prevent bone complications associated with this condition. This distinct mechanism not only has the potential to improve bone health but also may offer an alternative for patients who do not respond well to standard treatments like bisphosphonates. Researchers are excited about denosumab as it could provide a dual benefit: managing bone disease while also impacting cancer progression.

What evidence suggests that denosumab might be an effective treatment for multiple myeloma?

Research has shown that denosumab, the treatment under study in this trial, effectively treats multiple myeloma, a type of blood cancer. One study found that patients taking denosumab experienced a longer time before disease progression—46.1 months compared to 35.4 months for those taking zoledronate. Another study demonstrated that denosumab is safe and effective for patients with kidney problems, which are common in multiple myeloma. Overall, denosumab has delayed bone problems in multiple myeloma patients, making it a promising treatment option. ^{1 2 3 4 5}

Who Is on the Research Team?

Brea Lipe, MD

Principal Investigator

University of Rochester Wilmot Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with smoldering multiple myeloma (SMM) who meet specific health criteria, including normal organ function and a life expectancy of more than a year. They must be able to take daily calcium and vitamin D, have no history of certain bone treatments, and agree to use effective contraception.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

Subjects with reproductive potential must be willing to use 2 highly effective methods of contraception or practice sexual abstinence throughout the study and continue for 5 months after the study duration

Your vitamin D level must be 30 ng/mL or higher after treatment.

Exclusion Criteria

I have used IV bisphosphonates before or during the study.

I have or had bone disease in my jaw.

Evidence of any of the following conditions per subject self-report or medical chart review

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive denosumab 120mg subcutaneously every 4 weeks for 12 cycles

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Denosumab

Trial Overview The study tests the safety and potential effectiveness of denosumab in reducing the risk of developing active multiple myeloma in patients with SMM. It will also assess how well participants tolerate this medication.

How Is the Trial Designed?

Group I: Denosumab Experimental Treatment 1 Intervention

Denosumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Prolia for:

• Osteoporosis in postmenopausal women
• Bone loss associated with hormone ablation therapy for prostate cancer
• Bone loss associated with hormone ablation therapy for breast cancer

Approved in United States as Prolia for:

• Treatment of postmenopausal women with osteoporosis at high risk for fracture
• Treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
• Treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer

Approved in Canada as Prolia for:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture
• Treatment to increase bone mass in men with osteoporosis at high risk for fracture

Approved in Japan as Prolia for:

• Treatment of osteoporosis in postmenopausal women
• Treatment of bone loss associated with hormone ablation therapy for prostate cancer

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

Denosumab, a monoclonal antibody used to treat skeletal-related events in advanced cancer patients, shows dose-dependent pharmacokinetics, meaning its absorption and effects vary with the dose given, particularly at doses below 60 mg.

In patients with solid tumors and bone metastases, denosumab effectively reduces bone turnover markers quickly, and its pharmacokinetics and pharmacodynamics remain consistent across different tumor types and cancer treatments, indicating its broad applicability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and pharmacodynamics of denosumab in patients with advanced solid tumours and bone metastases: a systematic review. Sohn, W., Simiens, MA., Jaeger, K., et al.[2022]

Denosumab, a drug used to prevent bone loss, was linked to a non-healing area in the lower jaw after a tooth extraction, highlighting a potential complication associated with its use.

After stopping denosumab, the non-healing area healed successfully, suggesting that discontinuation of the drug may be necessary to allow for healing in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Denosumab: a case of MRONJ with resolution. Lyttle, CV., Patterson, H.[2018]

LY01011, a biosimilar to denosumab, showed pharmacokinetic (PK) and pharmacodynamic (PD) similarity to denosumab in a study involving 168 healthy Chinese subjects, indicating it may be an effective alternative for preventing skeletal-related events in patients with bone metastases.

The safety profiles of LY01011 and denosumab were comparable, with only a small number of treatment-emergent adverse events reported, none of which were related to the study drug, suggesting that LY01011 is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial comparing LY01011, biosimilar candidate, with the reference product denosumab (Xgeva®) in healthy Chinese subjects. Ding, Y., Liu, Y., Dou, C., et al.[2023]

Denosumab (XGEVA®) is a monoclonal antibody that effectively inhibits bone resorption by preventing the activation of osteoclasts, making it a targeted treatment for patients with bone metastases.

In Phase 3 clinical studies, denosumab was found to be superior to zoledronic acid in delaying skeletal-related events (SREs) by a median of 8.2 months, suggesting it may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative pharmacology of denosumab in patients with bone metastases from solid tumors. Perez Ruixo, JJ., Doshi, S., Sohn, W., et al.[2015]

Denosumab, a monoclonal antibody that inhibits RANKL, shows consistent pharmacokinetics across a large population of 1,076 subjects, including both healthy individuals and cancer patients, indicating its effectiveness in preventing osteoclast activation and survival.

The study found that after administering denosumab, over 95% of patients achieved more than 97% RANKL occupancy, suggesting that dosage adjustments based on body weight, age, race, or tumor type are unnecessary for patients with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. Gibiansky, L., Sutjandra, L., Doshi, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8857591/

Experience with denosumab (XGEVA®) for prevention of ... A meta-analysis of four trials showed that denosumab was significantly superior to zoledronate in delaying the incidence of first on-study SRE (HR, 0.86; 95% CI ...

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3343/533188/Evaluation-of-the-Safety-and-Efficacy-of-Denosumab

Evaluation of the Safety and Efficacy of Denosumab in ... Overall, our findings suggest that denosumab is effective and safe for MM patients with severe RI, provided that proactive measures are taken ...

3. xgevahcp.com xgevahcp.com/efficacy/multiple-myeloma-clinical-trial

Multiple Myeloma Clinical Trial | XGEVA® (denosumab) XGEVA® provided nearly 23 months of prevention · Median PFS was 46.1 months for XGEVA® compared with 35.4 months for ZA · All patients received standard of care ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5927995/

Denosumab for bone lesions in multiple myeloma In patients with giant cell tumors of the bone, an open label study with denosumab demonstrated a high level of efficacy: 96% of patients with surgically ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124060956

Evaluation of the Safety and Efficacy of Denosumab ... Our findings suggest that denosumab is effective and safe for MM patients with severe RI, provided that proactive measures are taken to mitigate hypocalcemia.