Denosumab in Treating Patients with Multiple Myeloma with Kidney Insufficiency

Inclusion Criteria

• Subjects must have documented multiple myeloma as defined by one or more of the criteria below: * Clonal bone marrow plasma cells >= 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following calcium, renal failure, anemia, bone lesions (CRAB) features and myeloma-defining events (MDEs) * Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: ** Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL) ** Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177 umol/L (> 2 mg/dL) ** Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L ** Bone lesions: one or more osteolytic lesion on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)/CT * Any one or more of the following biomarkers of malignancy (MDEs) ** 60% or greater clonal plasma cells on bone marrow examination ** Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved free light chain is at least 100 mg/L (a patient’s “involved” free light chain – either kappa or lambda – is the one that is above the normal reference range; the uninvolved light chain is the one that typically is in, or below, the normal range) ** More than one focal lesion on magnetic resonance imaging (MRI) that is at least 5 mm or greater in size
• Creatinine clearance < 30 mL/min, not eligible for bisphosphonate; estimated glomerular filtration rate will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and/or the Cockcroft-Gault equation
• Serum calcium or albumin-adjusted serum calcium >= 2.1 mmol/L (8.4 mg/dL) and =< 2.9 mmol/L (11.5 mg/dL) (reference range 8.5-10.8 mg/dL)
• Able to tolerate daily supplementation of calcium and vitamin D
• Must have a vitamin D level >= 30 ng/mL after repletion
• Total bilirubin =< 2.0 x institutional upper limit of normal (ULN)
• Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x institutional ULN
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
• Plan to receive anti-myeloma therapies
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy greater than 6 months
• Subjects with reproductive potential must be willing to use, in combination with his/her partner, 2 highly effective methods of effective contraception or practice sexual abstinence throughout the study and continue for 5 months after the study duration; subjects who are surgically sterile (e.g. history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy) are not required to use additional contraceptive measures
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Prior administration of denosumab
• Active intravenous (IV) bisphosphonate use in the last 3 months
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia
• Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw
• Active dental or jaw condition that requires oral surgery, including tooth extraction
• Non-healed dental/oral surgery, including tooth extraction
• Planned invasive dental procedures during the course of study
• Evidence of any of the following conditions per subject self-report or medical chart review * Any prior invasive malignancy within 5 years of enrollment that may affect outcome of study * Any non-invasive malignancy not treated with curative intent or with known active disease within 5 years before enrollment that may affect outcome of study * Major surgery or significant traumatic injury occurring within 4 weeks before enrollment * Active infection with hepatitis B virus or hepatitis C virus * Known infection with human immunodeficiency virus (HIV) * Active infection requiring IV anti-infective therapy
• Subject is pregnant or breast feeding, or planning to become pregnant within 5 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 5 months after the end of treatment
• Clinically significant hypersensitivity to denosumab or any components of denosumab 120 mg
• Known sensitivity to any of the products to be administered during the study (e.g., calcium, or vitamin D)
• Subject is receiving or is less than 14 days since ending other experimental drug (no marketing authorization for any indication)
• Any major medical or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results