Smoldering Multiple MyelomaPhase 2NCT03839459
Denosumab for Smoldering Multiple Myeloma
A Phase 2 study testing Denosumab in people with Smoldering Multiple Myeloma, run by University of Rochester at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Smoldering Multiple Myeloma
- What is being tested?
- Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Apr 2019to 30 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has confirmed SMM according to the definition of the International Myeloma Working Group (IMWG) definition: serum M-protein ≥3 g/dL or BMPC >10% but less than 60%, or both, along with normal organ and marrow function (CRAB) within 4 weeks prior to baseline. C: Absence of hypercalcemia, evidenced by a calcium ≤11 mg/dL. R: Absence of renal failure, evidenced by a creatinine ≤ 2.0mg/dL A: Absence of anemia, evidenced by a hemoglobin ≥10 g/dL.
- B: Absence of lytic bone lesions per IMWG recommendations:
- One of either PET-CT, low-dose whole-body CT (LDWBCT) or MRI of the whole body or spine. Increased uptake on PET-CT alone is not adequate for the diagnosis of multiple myeloma; evidence of underlying osteolytic bone destruction is needed on the CT portion of the examination.
- One of the risk factors below that portends for an increased risk of progression to MM:
- An abnormal free light chain ratio
- M-spike ≥ 4 g/dL
Show all 22Show fewer
- ≥ 50% bone marrow plasma cells
- Immunoparesis ≥ 20% less than the institutional normal standard of the uninvolved immunoglobulins
- Serum calcium or albumin-adjusted serum calcium ≥ 2.1 mmol/L (8.4 mg/dL) and ≤ 2.9mmol/L (11.5 mg/dL) (Reference range 8.5-10.8 mg/dL)
- Able to tolerate daily supplementation of calcium and vitamin D
- Must have a vitamin D level ≥ 30 ng/mL after repletion
- Participants must have normal organ as defined below:
- Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN); patients diagnosed with Gilbert's syndrome can enroll with a total bilirubin > 2 after review of the principal investigator
- AST(SGOT) ≤2.5 × institutional ULN
- ALT(SGPT) ≤2.5 × institutional ULN
- Age ≥ 18 years.
- ECOG PS ≤1
- Life expectancy greater than 12 months
- Subjects with reproductive potential must be willing to use, in combination with his/her partner, 2 highly effective methods of effective contraception or practice sexual abstinence throughout the study and continue for 5 months after the study duration. Subjects who are surgically sterile (e.g. history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy) are not required to use additional contraceptive measures.
- Ability to understand and the willingness to sign a written informed consent document.
- -Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Statement on Inclusion of Women and Minorities - Men and women of all ethnicities and racial backgrounds are eligible for this study.
Who cannot join
- Prior administration of denosumab.
- Any history of IV bisphosphonate use prior to or during the study
- Prescription oral fluorides or bisphosphonate usage > 3 months within the past 2 years
- Systemic corticosteroids > 10mg prednisone per day
- Known secondary cause for osteopenia or osteoporosis
- Patient has symptomatic MM, as defined by any of the following:
Show all 30Show fewer
- Lytic lesions or pathologic fractures.
- Anemia (hemoglobin <10 g/dL)
- Hypercalcemia (corrected serum calcium > 11.0 mg/dL)
- Renal insufficiency (creatinine > 2.0 mg/dL).
- Clonal bone marrow plasma cells > 60%
- An involved serum free light chain (kappa or Lambda) > 100mg/L with the ratio of the involved/uninvolved free light chains also > 100 mg/L
- One or more osteolytic lesions on radiography, but more than one lesion is required if < 10% marrow plasma cells. From MRI imaging, there must be more than one lesion of > 5mm in size.
- Other: symptomatic hyperviscosity, amyloidosis, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein)
- Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.
- Active dental or jaw condition that requires oral surgery, including tooth extraction.
- Non-healed dental/oral surgery, including tooth extraction.
- Planned invasive dental procedures during the course of study.
- Evidence of any of the following conditions per subject self-report or medical chart review:
- Any prior invasive malignancy within 3 years of enrollment that may affect outcome of study
- Any non-invasive malignancy not treated with curative intent or with known active disease within 3 years before enrollment that may affect outcome of study
- Major surgery or significant traumatic injury occurring within 4 weeks before enrollment
- Active infection with Hepatitis B virus or Hepatitis C virus
- Known infection with human immunodeficiency virus (HIV) requiring IV anti-infective therapy
- Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment.
- Female subject of child-bearing potential is not willing to use, in combination with her partner, 2 methods of highly effective contraception during treatment and for 5 months after the end of treatment.
- Clinically significant hypersensitivity to denosumab or any components of denosumab 120mg.
- Known sensitivity to any of the products to be administered during the study (e.g., calcium, or vitamin D).
- Subject is receiving or is less than 14 days since ending other experimental drug (no marketing authorization for any indication).
- Any major medical or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
This is an open label, Phase II trial of denosumab 120mg subcutaneous (SC) for patients with smoldering multiple myeloma (SMM). Subjects will be recruited from the James P. Wilmot Cancer Center, University of Rochester in Rochester, New York. Patients seen in the inpatient or outpatient setting with histologically confirmed SMM will be evaluated for this study.
20 patients will be treated as follows: Denosumab: day 1 = 120mg SC every 4 weeks for 12 cycles. Cycles will be 28 days in length. Patients will be followed after completion of the study per standard of care for progression free survival for an additional 2 years after the last dose of denosumab. All patients will take daily vitamin D and calcium supplements of at least 1200mg elemental calcium and 800IU of vitamin D unless documented hypercalcemia develops on study. Pre-existing hypocalcemia must be corrected prior to initiating therapy with denosumab. Serum vitamin D levels will be checked during screening and should be repleted to a total 25-hydroxyvitamin D level ≥30ng/mL.
- Conditions
- Smoldering Multiple Myeloma
- Being tested
- Denosumab
- Keywords
- Smoldering Multiple Myeloma, Denosumab
- Medical subject headings
- Smoldering Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
120mg of Denosumab will be administered subcutaneously once every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Denosumab | Experimental | Not described Receives: Drug: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Subjects With a Downgraded Risk of Progression of Smoldering Multiple Myeloma if the Risk Category Decreases.
Risk Categories:
Low Risk:Patient has SMM, but none of the listed risk factors Low-Intermediate Risk: 1 risk factor is present High-Intermediate Risk: 2 risk factors are present High Risk: 3 risk factors are present
Risk Factors:
- BM plasma cell % ≥50
- M-protein ≥ 3g/dL
- Involved/ un-involved free light chains ≥ 8
Measured: 1 year
Secondary outcomes (4)
Proportion of Participants With Skeletal Related Events
Skeletal related events were defined as pathological fractures, radiation to bone, surgery to bone, or fractures requiring stabilization, confirmed by imaging. Participants were counted once if they experienced at least one skeletal related event during the 1 year follow up period.
Measured: 1 year
Proportion of Participants With Progression to Multiple Myeloma
Progression to multiple myeloma was assessed according to International Myeloma Working Group criteria during the 1 year follow up period following treatment initiation.
Measured: 1 year
Proportion of Participants With Progression Free Survival at 3 Years
Progression free survival was defined as the absence of disease progression or death from any cause at the 3 year assessment time point.
Measured: 3 years
Proportion of Participants With Change in Bone Mineral Density From Screening to 1 Year
Bone mineral density was assessed using dual energy X ray absorptiometry scans at screening and approximately 1 year after treatment initiation. Participants with evaluable scans within the protocol specified assessment window were included in the analysis.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start19 Apr 2019
- Primary completion16 Sep 2022
- Study completion30 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Smoldering Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Brea Lipe, University of Rochester
- Investigators
- Brea Lipe, Principal investigator, University of Rochester Wilmot Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03839459
- Sponsor's protocol ID
- UMMY18121
- Status last verified
- May 2026
- First submitted
- 11 Feb 2019
- Last updated
- 15 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Denosumab for Smoldering Multiple Myeloma
- ClinicalTrials.gov ID
- NCT03839459
- Acronym / sponsor ID
- UMMY18121
- Conditions
- Smoldering Multiple Myeloma
- Keywords
- Smoldering Multiple Myeloma, Denosumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 19 Apr 2019 (actual)
- Primary completion
- 16 Sep 2022 (actual)
- Study completion
- 30 Jan 2025 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Posted 15 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an open label, Phase II trial of denosumab 120mg subcutaneous (SC) for patients with smoldering multiple myeloma (SMM). Subjects will be recruited from the James P. Wilmot Cancer Center, University of Rochester in Rochester, New York. Patients seen in the inpatient or outpatient setting with histologically confirmed SMM will be evaluated for this study.
20 patients will be treated as follows: Denosumab: day 1 = 120mg SC every 4 weeks for 12 cycles. Cycles will be 28 days in length. Patients will be followed after completion of the study per standard of care for progression free survival for an additional 2 years after the last dose of denosumab. All patients will take daily vitamin D and calcium supplements of at least 1200mg elemental calcium and 800IU of vitamin D unless documented hypercalcemia develops on study. Pre-existing hypocalcemia must be corrected prior to initiating therapy with denosumab. Serum vitamin D levels will be checked during screening and should be repleted to a total 25-hydroxyvitamin D level ≥30ng/mL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Experimental | Drug: Denosumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patient has confirmed SMM according to the definition of the International Myeloma Working Group (IMWG) definition: serum M-protein ≥3 g/dL or BMPC >10% but less than 60%, or both, along with normal organ and marrow function (CRAB) within 4 weeks prior to baseline. C: Absence of hypercalcemia, evidenced by a calcium ≤11 mg/dL. R: Absence of renal failure, evidenced by a creatinine ≤ 2.0mg/dL A: Absence of anemia, evidenced by a hemoglobin ≥10 g/dL.
- One of either PET-CT, low-dose whole-body CT (LDWBCT) or MRI of the whole body or spine. Increased uptake on PET-CT alone is not adequate for the diagnosis of multiple myeloma; evidence of underlying osteolytic bone destruction is needed on the CT portion of the examination.
- One of the risk factors below that portends for an increased risk of progression to MM:
- Serum calcium or albumin-adjusted serum calcium ≥ 2.1 mmol/L (8.4 mg/dL) and ≤ 2.9mmol/L (11.5 mg/dL) (Reference range 8.5-10.8 mg/dL)
- Able to tolerate daily supplementation of calcium and vitamin D
Key exclusion criteria (30 listed)
- Prior administration of denosumab.
- Any history of IV bisphosphonate use prior to or during the study
- Prescription oral fluorides or bisphosphonate usage > 3 months within the past 2 years
- Systemic corticosteroids > 10mg prednisone per day
- Known secondary cause for osteopenia or osteoporosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Denosumab120mg of Denosumab will be administered subcutaneously once every 4 weeks | Drug | Denosumab |
Primary outcome
Proportion of Subjects With a Downgraded Risk of Progression of Smoldering Multiple Myeloma if the Risk Category Decreases.
Time frame: 1 year
Risk Categories: Low Risk:Patient has SMM, but none of the listed risk factors Low-Intermediate Risk: 1 risk factor is present High-Intermediate Risk: 2 risk factors are present High Risk: 3 risk factors are present Risk Factors: 1. BM plasma cell % ≥50 2. M-protein ≥ 3g/dL 3. Involved/ un-involved free light chains ≥ 8
4 secondary outcomes
Proportion of Participants With Skeletal Related Events
Time frame: 1 year
Proportion of Participants With Progression to Multiple Myeloma
Time frame: 1 year
Proportion of Participants With Progression Free Survival at 3 Years
Time frame: 3 years
Proportion of Participants With Change in Bone Mineral Density From Screening to 1 Year
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)
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Smoldering Multiple Myeloma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brea Lipe principal investigator
University of Rochester Wilmot Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab in people with Smoldering Multiple Myeloma, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Subjects With a Downgraded Risk of Progression of Smoldering Multiple Myeloma if the Risk Category Decreases. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.