Denosumab for high risk SMM and SLiM CRAB positive, early myeloma patient- a randomized, placebo controlled phase II trial DEFENCE” (DEnosumab For the rEductioN of the smoldering myeloma transformatioN inCidence ratE)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 8

Inclusion Criteria

•Age = 18 years
•Able to provide written informed consent in accordance with federal, local, and institutional guidelines
•Must meet criteria of high risk smoldering MM or early SLiM CRAB MM based on the criteria described below:
oHigh-risk SMM is defined here according to the revised Mayo Clinical algorithm (2 out of 3 criteria must be fulfilled):
•Bone marrow clonal plasma cells >20%
•Serum M protein >2.0g/dL
•Serum free light chain ratio >20 measured with Binding site Kit”
oEarly ‘SLiM CRAB’ multiple myeloma (3)
Patients must present with only one of the following features
•Bone marrow clonal plasma cells = 60%, or
•Serum FLC ratio = 100 (k-LC leading) or = 0.01 (l-LC leading), measured with Binding site Kit”, or
•>1 Focal bone lesion of =5mm (not associated with osteolysis, detected by PET-CT or whole-body low-dose CT (WBLDCT))
• Time from diagnosis of high risk SMM or SLIM CRAB positive, early MM to study enrollment: <5 years
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

•ECOG >3
•Active, symptomatic MM (fulfilling CRAB-criteria)
•Non secretory MM, extramedullary plasmacytoma, plasma cell leukemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
•MGUS
•Hypocalcemia (can be corrected by drug intervention before start of treatment)
•Second malignancy within the past 5 years except:
oAdequately treated basal cell or squamous cell skin cancer
oCarcinoma in situ of the cervix
oProstate cancer Gleason score = 6 with stable prostate-specific antigen (PSA over 12 months)
oDuctal breast carcinoma in situ with full surgical resection (i.e., negative margins)
oTreated medullary or papillary thyroid cancer
oSimilar condition with an expectation of > 95% five-year disease-free survival
•Active infection within the 14 days prior to randomization requiring systemic antibiotics and/or antiviral therapy
•Known human immunodeficiency virus (HIV) seropositivity or active hepatitis C or hepatitis B infection (subjects with past hepatitis B virus [HBV] infection or resolved HBV infection defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti HBc] antibody test are eligible; subjects positive for hepatitis C virus [HCV] antibody are eligible only if polymerase chain reaction [PCR] is negative for HCV RNA.)
•Participation in another interventional study within the 28 days prior to randomization
•Any other clinically significant medical disease or social condition that, in the investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent, be compliant with study procedures, or provide accurate information.
•Prior administration of denosumab
•Prior exposure to any experimental or approved anti-myeloma agent
•Use of oral bisphosphonates with a cumulative exposure of more than 1 year (wash out period for allowed bisphosphonate exposure 1 month)
•More than 1 previous dose of IV bisphosphonate administration or teriparatide (wash out period for allowed bisphosphonate exposure 1 month)
•Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
•Active dental or jaw condition which requires oral surgery, including tooth extraction
•Subject is pregnant or breast feeding, or planning to become pregnant within 7 months after the end of treatment
•Female subject of child bearing potential is not willing to use, in combination with her partner, a highly effective and in addition an effective contraception during treatment and for 5 months after the end of treatment
•Known sensitivity to denosumab (including all components of the formulation) or any of the products to be administered during the study (e.g. mammalian derived products, calcium, or vitamin D)
•Subject is receiving or is less than 30 days since ending other experimental device or drug (no marketing authorization for any indication).
•Subject will not be available for follow-up assessment

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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