Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma

Monoclonal Gammopathy of Undetermined Significance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02726750
• Other study ID #: PA15-0575
• Secondary ID: NCI-2020-07336PA
• Status: Recruiting
• Start date: December 14, 2015
• Est. completion date: April 30, 2025

Study information

• Verified date: November 2023
• Source: M.D. Anderson Cancer Center
• Contact: Mei Huang
• Phone: 713-745-9901
• Email: mhuang3[@]mdanderson.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Monoclonal Gammopathy of Undetermined Significance
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Paraproteinemias
• Smoldering Multiple Myeloma
• Smoldering Plasma Cell Myeloma

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood samples

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Molecular profiling analysis of patients who develop MM	Analysis will include whole exome sequencing and gene expression profiling and cellular (including flow cytometry) profiling using bone marrow and peripheral blood samples.	3 years
Other	Immune characterization of patients who develop MM	Analysis will include cell surface and functional studies of dendritic, T-, B-, natural killer (NK)- and NKT-cells using peripheral blood samples.	3 years
Other	Immune characterization of patients who develop MM	Analysis will include cell surface and functional studies of dendritic, T-, B-, NK- and NKT-cells using bone marrow samples.	3 years
Primary	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
Primary	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
Primary	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	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
Secondary	Molecular and genetic profile analysis	Will study the correlation of molecular and genetic profiles with time to MM progression.	3 years

External Links

•   University of Texas MD Anderson Cancer Center Website