A Study of Denosumab in Multiple Myeloma Patients With Renal Insufficiency

Study Overview
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Brief Summary
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This research study is studying a possible therapy as a possible treatment for the consequences of Multiple Myeloma with renal insufficiency.

Detailed Description
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This research study is a Phase II clinical trial. This study will assess the safety and tolerability of denosumab in Multiple Myeloma participants, by studying drug interactions with different parts of the body. The FDA (the U.S. Food and Drug Administration) has not approved Denosumab for this specific disease but it has been approved denosumab for use in other cancers to treat cancer-related bone disease such as prostate and breast cancer.

Official Title
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A Phase 2, Single-Arm Study of Denosumab in Multiple Myeloma Patients With Renal Insufficiency

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Denosumab Q4W


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic MM as defined by IMWG requiring anti-myeloma therapy. Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma Monoclonal protein present in the serum and/or urine Creatinine clearance < 30 mL/min, not eligible for bisphosphonate. Estimated glomerular filtration rate will be calculated using 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 Vitamin D level ≥ 30 ng/mL after repletion Participants must have normal organ as defined below: Total bilirubin ≤ 2.0 x ULN AST(SGOT) ≤2.5 × institutional upper limit of normal ALT(SGPT) ≤2.5 × institutional upper limit of normal Plan to receive anti-myeloma therapies. Age ≥ 18 years. ECOG performance status ≤ 2 Life expectancy greater than 6 months 0-3 lines of prior anti-myeloma therapy. 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 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 which 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab Injection<br>Patients will be administered Denosumab Q4W at a pre-determine dose for 12 cycles. Denosumab Q4W is administered by subcutaneous injection. | Drug: Denosumab Q4W<br> <br> * Other names: Prolia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change Of sCTX Levels |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change In Bone Mineral Density |  | 2 years | 
| Percent Change In uNTX Levels |  | 2 years | 
| Subject Incidence Of Hypocalcemia |  | 2 years | 
| Subject Incidence Of Occurrence Of Documented SRE At 12 Months |  | 2 years | 
| Subject Incidence Of Adverse Events |  | 2 years | 
| Percent Change In Bone Turnover Markers |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma