Observational Prospective Research Study In Monoclonal Gammopathies leadINg to Myeloma

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

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.

Study Overview

• Status: Recruiting
• Conditions: Monoclonal Gammopathy of Undetermined Significance; Smoldering Plasma Cell Myeloma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Biospecimen Collection

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Mei Huang; Phone Number: 713-745-9901; Email: mhuang3@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Principal Investigator: Krina Patel, MD
      • Contact: Mei Huang; Phone Number: 713-745-9901; Email: mhuang3@mdanderson.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with monoclonal gammopathy of unknown significance and/or smoldering multiple myeloma

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observational (biospecimen collection); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Biospecimen Collection; Undergo collection of blood samples

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Krin Patel, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2015
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: April 1, 2016
• First Posted (Estimated): April 4, 2016

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Hematologic Diseases; Immunoproliferative Disorders; Precancerous Conditions; Paraproteinemias; Blood Protein Disorders; Hypergammaglobulinemia; Hemic and Lymphatic Diseases; Smoldering Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance
• Other Study ID Numbers: PA15-0575 (Other Identifier: M D Anderson Cancer Center); NCI-2020-07336 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No