Denosumab for Smoldering Multiple Myeloma

NCT03839459 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: UMMY18121
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Smoldering Multiple Myeloma

Keywords

Smoldering Multiple Myeloma; Denosumab

Outcome Measures

Primary Outcomes (1)

• 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: 1. BM plasma cell % ≥50 2. M-protein ≥ 3g/dL 3. Involved/ un-involved free light chains ≥ 8

  1 year

Secondary Outcomes (4)

• Proportion of Subjects With Skeletal Related Events

  1 year

• Proportion of Subjects With Disease Progression to Multiple Myeloma

  1 year

• Proportion of Subjects With Progression Free Survival

  3 year

• Proportion of Subjects With Change in Bone Mineral Density

  1 year

Study Arms (1)

Denosumab

EXPERIMENTAL

Drug: Denosumab

Interventions

Denosumab DRUG

120mg of Denosumab will be administered subcutaneously once every 4 weeks

Denosumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ≥ 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

You may not qualify if:

• 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:
• 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.

Sponsors & Collaborators

• University of Rochester: lead
• Amgen: collaborator

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Brea Lipe, MD
• Organization: University of Rochester Medical Center

Brea_Lipe@URMC.Rochester.edu

(585) 275-4099

Study Officials

• Brea Lipe

  University of Rochester Wilmot Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor - Department of Medicine , Hematology/Oncology

Study Record Dates

• First Submitted: February 11, 2019
• First Posted: February 15, 2019
• Study Start: April 19, 2019
• Primary Completion: September 16, 2022
• Study Completion: January 30, 2025
• Last Updated: January 28, 2026
• Results First Posted: February 15, 2023

Record last verified: 2025-09

Locations

US (1)