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

• Status: Active, not recruiting
• Trial end date: 2024-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
• Collaborators: Amgen; Assign Data Management and Biostatistics GmbH
• Treatments: Denosumab; Pharmaceutical Solutions

Criteria

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:

• High-risk SMM is defined here according to the revised Mayo Clinical criteria (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"

• 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

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:

• Adequately treated basal cell or squamous cell skin cancer

• Carcinoma in situ of the cervix

• Prostate cancer Gleason score ≤ 6 with stable prostate-specific antigen (PSA over 12 months)

• Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)

• Treated medullary or papillary thyroid cancer

• 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 (washout period for allowed bisphosphonate exposure 1 month)

• More than 1 previous dose of IV bisphosphonate or teriparatide administration (washout 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 breastfeeding, or planning to become pregnant within 7 months after the end of treatment

• Female subject of childbearing potential is not willing to use, in combination with her partner, a highly effective and in addition an effective method of 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 (eg, mammalian derived products, calcium, or vitamin D)

• Subject is receiving or is less than 30 days since ending other experimental devices or drugs (no marketing authorization for any indication).

• Subject will not be available for follow-up assessment