A Phase 2 interventional study of Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA] and Placebo 1.7 ml Subcutaneous Solution in Multiple Myeloma, sponsored by Arbeitsgemeinschaft medikamentoese Tumortherapie. Completed at 10 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-11.
Sponsored by Arbeitsgemeinschaft medikamentoese Tumortherapie · Phase 2, Interventional, and Prevention
This is a randomized, 2-arm phase II, placebo-controlled, multi-center study, where the investigators aim to evaluate whether the reported benefits of denosumab, delay of SRE and decrease in myeloma growth promotion, reduce the risk of progression of high-risk SMM and of early 'SLiM CRAB' myeloma into active, symptomatic CRAB positive myeloma or serological progression. In addition, tolerability of long-term treatment will be assessed.
The aim of this study is to evaluate whether the transition of early Multiple Myeloma (High Risk Smouldering Multiple Myeloma SMM or "Ultra High Risk" SMM) or SLiM CRAB positive multiple myeloma to a symptomatic multiple myeloma (MM) can be reduced or delayed by the administration of denosumab.
With the exception of clinical studies, there are currently no standardized treatment options for SMM. Ultra-high risk SMM is already part of early active myeloma and is therefore in some cases treated according to a standard myeloma protocol (Revlimid-Dexamethasone, Velcade melphalan prednisone, melphalan prednisone thalidomide, or others). However, most practitioners recommend a wait-and-see strategy, since depending on the initial situation within two years only 58-95% of patients develop an 'active' MM and 5-42% of the patients had a stable disease and therefore do not necessarily have to be treated immediately.
Denosumab is a human monoclonal antibody (IgG2) which binds to RANKL with high affinity and specificity. RANKL (receptor activator of NF-κB Ligand) is a protein that is responsible for the formation, function and survival of osteoclasts (cell type responsible for bone resorption) Increased osteoclast activity, stimulated by RANKL, is a key mediator of the bone resorption in bone metastases and MM. Thus the activity of denosumab is resulting in a reduced number and function of osteoclasts and thus decreases the bone resorption and tumor-induced bone destruction.
After an initial phase of about 14 days (screening), the patients will be randomized 1:1 in one of the two study groups (arm A: denosumab or arm B: placebo). The study is double-blinded. The planned duration of therapy is 3 years. Patients receive denosumab or placebo every 4 weeks for 6 months, then every 3 months until a total of 3 years or progression.
After completion of the therapy, an observation and follow-up phase is carried out with patient visits every 3 months until the end of the treatment.
3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.
This study's enrollment of 8 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →Arbeitsgemeinschaft medikamentoese Tumortherapie is the lead sponsor of 43 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Must meet criteria of high-risk smoldering MM or early "SLiM CRAB" MM based on the criteria described below:
High-risk SMM is defined here according to the revised Mayo Clinical criteria (2 out of 3 criteria must be fulfilled):
Early 'SLiM CRAB' multiple myeloma
Exclusion Criteria:
Second malignancy within the past 5 years except:
Denosumab 120 MG/1.7 ML Subcutaneous Solution \[XGEVA\] Every 4 weeks (Q4W) for 6 months then every 3 months (Q3M) for a total of 3 years or until progression to active, symptomatic MM Calcilac 500 mg/400 I.E. (Calcium/Vitamin D3) Concomitant medication, oral, 1 chewable tablet / day
Drug: Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]
Placebo 1.7 ml Subcutaneous Solution SC every 4 weeks (Q4W) for 6 months then every 3 months (Q3M) for a total of 3 years or until progression to active, symptomatic MM Calcilac 500 mg/400 I.E. (Calcium/Vitamin D3) Concomitant medication, oral, 1 chewable tablet / day
Drug: Placebo 1.7 ml Subcutaneous Solution
Administration every 4 weeks (Q4W) for 6 months then every 3 months (Q3M) for a total of 3 years or until progression to active, symptomatic MM
Administration every 4 weeks (Q4W) for 6 months then every 3 months (Q3M) for a total of 3 years or until progression to active, symptomatic MM
Time to progression
Time from randomization to transformation to symptomatic, active MM (defined as progression to active multiple myeloma according to IMWG diagnosis criteria 2014) or progression of disease according to IMWG response criteria 2016
Time frame: 78 months (the first 6 cycles are 28 days, thereafter each cycle is 3 months for a maximum of 36 months)
Percentage of patients transforming in 3 years
Percentage of patients with high-risk SMM and early 'slim CRAB' positive MM transforming to CRAB positive multiple myeloma and/or developing serological progression (as defined by IMWG criteria 2016 for MM) within 3 years
Time frame: 36 months (the first 6 cycles are 28 days, thereafter each cycle is 3 months)
Overall survival
To determine the overall survival of patients receiving either denosumab or placebo
Time frame: 78 months (the first 6 cycles are 28 days, thereafter each cycle is 3 months for a maximum of 36 months)
Time to first skeletal-related event
To determine the time to first skeletal-related event for patients receiving either denosumab or placebo. • Imaging: low dose wbCT (details will be described in a separate guidance document) or PET-CT mandatory
Time frame: 78 months (baseline and every 6 months thereafter until progression or maximum of 3 years).
Incidence of bone lesions as MM defining events
To determine the incidence of bone lesions as MM defining events. • Imaging: low dose wbCT (details will be described in a separate guidance document) or PET-CT mandatory.
Time frame: 78 months (baseline and every 6 months thereafter until progression or maximum of 3 years).
Time to first anti-myeloma treatment
To determine the time to first anti-myeloma treatment for patients receiving either denosumab or placebo
Time frame: 78 months (the first 6 cycles are 28 days, thereafter each cycle is 3 months for a maximum of 36 months)
Plan to share: No
This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
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Arbeitsgemeinschaft medikamentoese Tumortherapie