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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Denosumab for treating multiple myeloma?

Denosumab has been shown to be effective in preventing bone complications in patients with bone metastases from solid tumors, which suggests it might help with similar bone issues in multiple myeloma. It works by stopping the cells that break down bone, potentially reducing bone damage. ^{1 2 3 4 5}

Is denosumab generally safe for humans?

Denosumab has been used safely in patients with bone metastases from solid tumors and in those with multiple myeloma, but there is a risk of a condition called MRONJ (medication-related osteonecrosis of the jaw), which can occur after dental procedures. This condition resolved after stopping the drug. ^{1 2 3 4 6}

How is the drug denosumab unique in treating multiple myeloma?

Denosumab is unique because it is a fully human monoclonal antibody that targets RANKL, a protein involved in bone breakdown, which helps prevent bone complications. Unlike some other treatments, it is administered as a subcutaneous injection every four weeks, offering a different approach to managing bone-related issues in multiple myeloma. ^{1 2 3 5 7}

What is the purpose of this trial?

This study will assess the safety and tolerability of denosumab in smoldering multiple myeloma subjects as well to see if denosumab can reduce subjects' risk of getting multiple myeloma.

Research Team

Brea Lipe, MD

Principal Investigator

University of Rochester Wilmot Cancer Center

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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, 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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis of denosumab in patients with bone metastases from solid tumours. [2021]

2. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics and pharmacodynamics of denosumab in patients with advanced solid tumours and bone metastases: a systematic review. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized trial comparing LY01011, biosimilar candidate, with the reference product denosumab (Xgeva®) in healthy Chinese subjects. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Denosumab: a case of MRONJ with resolution. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Quantitative pharmacology of denosumab in patients with bone metastases from solid tumors. [2015]

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

Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis. [2022]

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

The use of denosumab in the setting of acute pathological fracture through giant cell tumour of bone. [2021]