Clinical and Genomic Predictors of Progression to Myeloma in Patients With Asymptomatic Monoclonal Gammopathies

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT02726750
Collaborator
National Cancer Institute (NCI) (NIH)
200
1
84
2.4

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Biospecimen Collection
  • Other: Laboratory Biomarker Analysis

Detailed Description

PRIMARY OBJECTIVE:
  1. To determine the rate of progression to multiple myeloma after 3 years of follow up.
SECONDARY OBJECTIVES:
  1. 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 Design

Study Type:
Observational
Anticipated Enrollment :
200 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Prospective Observational Study of Clinical and Genomic Predictors of Progression to Myeloma in Asymptomatic Monoclonal Gammopathies
Actual Study Start Date :
Dec 14, 2015
Anticipated Primary Completion Date :
Dec 15, 2021
Anticipated Study Completion Date :
Dec 15, 2022

Arms and Interventions

Arm 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.

Procedure: Biospecimen Collection
Undergo collection of blood samples

Other: Laboratory Biomarker Analysis
Correlative studies

Outcome Measures

Primary Outcome Measures

  1. Rate of progression to multiple myeloma (MM) [3 years]

    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.

  2. Progression free survival [3 years]

    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. Overall survival [3 years]

    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.

Secondary Outcome Measures

  1. Baseline patient characteristics and clinical variables [Baseline]

    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.

  2. Molecular and genetic profile analysis [3 years]

    Will study the correlation of molecular and genetic profiles with time to MM progression.

Other Outcome Measures

  1. Molecular profiling analysis of patients who develop MM [3 years]

    Analysis will include whole exome sequencing and gene expression profiling and cellular (including flow cytometry) profiling using bone marrow and peripheral blood samples.

  2. Immune characterization of patients who develop MM [3 years]

    Analysis will include cell surface and functional studies of dendritic, T-, B-, natural killer (NK)- and NKT-cells using peripheral blood samples.

  3. Immune characterization of patients who develop MM [3 years]

    Analysis will include cell surface and functional studies of dendritic, T-, B-, NK- and NKT-cells using bone marrow samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 M D Anderson Cancer Center Houston Texas United States 77030

Sponsors and Collaborators

  • M.D. Anderson Cancer Center
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Elisabet E Manasanch, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT02726750
Other Study ID Numbers:
  • PA15-0575
  • NCI-2020-07336
  • PA15-0575
First Posted:
Apr 4, 2016
Last Update Posted:
Oct 6, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 6, 2021