NCT03792763

Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients

Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients- a Randomized, Placebo Controlled Phase II Trial "DEFENCE" (DEnosumab For the rEductioN of the Smoldering Myeloma transformatioN inCidence ratE)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]	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
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

Timeline

• Start date: 2019-09-30
• Primary completion: 2023-09-14
• Completion: 2023-09-14
• First posted: 2019-01-03
• Last updated: 2025-02-11

Locations

10 sites across 3 countries: Austria, Germany, Israel