Denosumab for the reduction of the smouldering myeloma transformation incidence rate.
- Conditions
- High-risk smouldering multiple myeloma or SLiM CRAB positive earlymultiple myelomaMedDRA version: 21.1Level: LLTClassification code 10067386Term: Multiple myeloma transformationSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10075894Term: Smoldering myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000924-32-GB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 144
Each patient must meet all of the following inclusion criteria to be enrolled in the study:
• 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:
o High-risk SMM is defined here according to the conventional Mayo Clinical algorithm
• Bone marrow clonal plasma cells =10%
• Serum M protein =3.0g/dL
• Serum free light chain ratio < 0.125 (but > 0.01) or =8 (but <100), measured with Binding site Kit”
o Early ‘SLiM CRAB’ multiple myeloma
? Patients must present with only one of the following features
• Bone marrow clonal plasma cells =60%, or
• Serum FLC ratio =100 (kappa-LC leading) or =0.01 (lambda-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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0
Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
• 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:
o Adequately treated basal cell or squamous cell skin cancer
o Carcinoma in situ of the cervix
o Prostate cancer Gleason score =6 with stable prostate-specific antigen (PSA over 12 months)
o Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)
o Treated medullary or papillary thyroid cancer
o Similar 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
* Patients with known active or latent tuberculosis
• 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 or teriparatide administration (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, 2 methods of highly effective contraception during treatment and for 7 months after the end of treatment
• Male subject with partner of child bearing potential partner is not willing to use, in combination with his partner, 2 methods of highly effective contraception during treatment and for 10 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