Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma

Study Overview
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Brief Summary
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The goal of this study is to find markers that may help to predict why some patients who have monoclonal gammopathy of unknown significance (MGUS) or smoldering multiple myeloma (SMM) that have no signs or symptoms of disease (asymptomatic) develop multiple myeloma, while others do not. Studying markers such as age, level of proteins in blood, percent of abnormal blood cells in the bone marrow, genes in the abnormal blood cells, and bone abnormalities may help researchers to validate clinical and genomic predictors for future use in clinical practice.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the rate of progression to multiple myeloma after 3 years of follow up. SECONDARY OBJECTIVES: I. To describe baseline patient characteristics and clinical variables. II. To identify molecular and genetic correlates that may predict for progression to multiple myeloma (MM). OUTLINE: Patients undergo collection of blood samples every 6 months for 3 years. Patients may also undergo a biopsy, x-rays, positron emission tomography (PET)/computed tomography (CT) scans, and/or magnetic resonance imaging (MRI) scans to check the status of disease at the discretion of the treating physician. After completion of 3 years on study, patients are followed up every 6-12 months thereafter.

Official Title
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Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma (ORIGIN Study)

Conditions
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Monoclonal Gammopathy of Undetermined Significance, Smoldering Plasma Cell Myeloma

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with monoclonal gammopathy of unknown significance. Both criteria must be met: Serum monoclonal protein < 3 g/dL or urinary monoclonal protein < 500 mg per 24 hours and clonal bone marrow plasma cells < 10% Absence of myeloma defining events or amyloidosis Patients with smoldering multiple myeloma. Both criteria must be met: Serum monoclonal protein >= 3 g/dL or urinary monoclonal protein >= 500 mg per 24 hours and/or clonal bone marrow plasma cells 10-60% Absence of myeloma defining events or amyloidosis Exclusion Criteria: Evidence of myeloma defining events or biomarkers of malignancy due to underlying plasma cell proliferative disorder meeting at least one of the following 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/min or serum creatinine > 2 mg/dL Anemia: hemoglobin value < 10 g/dL or 2 g/dL < normal reference Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography CT (PET-CT) Clonal bone marrow plasma cell percentage >= 60% Involved:uninvolved serum free light chain ratio >= 100 measured by Freelite assay (The Binding Site Group, Birmingham, United Kingdom [UK]) > 1 focal lesions on magnetic resonance imaging (MRI) studies (each focal lesion must be 5 mm or more in size) Prior or concurrent systemic treatment for asymptomatic monoclonal gammopathies Bisphosphonates are permitted Radiotherapy is not permitted Prior treatment with chemotherapy or investigational agents for asymptomatic gammopathies is not permitted Plasma cell leukemia Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (biospecimen collection)<br>Patients undergo collection of blood samples every 6 months for 3 years. Patients may also undergo a biopsy, x-rays, PET/CT scans, and/or MRI scans to check the status of disease at the discretion of the treating physician. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of progression to multiple myeloma (MM) | Kaplan-Meier method will be used to estimate time to MM progression. Log-rank test will be used to evaluate the difference in rate of progression between/among patient groups. | 3 years | 
| Progression free survival | Will be estimated using the Kaplan-Meier method. Log-rank test will be used to evaluate the difference in rate of progression free survival between/among patient groups. | 3 years | 
| Overall survival | Will be estimated using the Kaplan-Meier method. Log-rank test will be used to evaluate the difference in rate of overall survival between/among patient groups. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline patient characteristics and clinical variables | Summary statistics including mean, standard deviation, median, and range will be provided for continuous variables. Frequency counts and percentages will be used to summarize categorical variables. | Baseline | 
| Molecular and genetic profile analysis | Will study the correlation of molecular and genetic profiles with time to MM progression. | 3 years |