Dysregulation of Glutamine Activity in the Pathogenesis of Multiple Myeloma

Not Applicable

Completed

• Conditions: Plasma Cell Myeloma; Monoclonal Gammopathy of Undetermined Significance
• Interventions: Other: 5-Carbon C 13-labeled Glutamine; Procedure: Biospecimen Collection; Other: Uniformly-labeled [13C]glucose

• Registration Number: NCT03119883
• Lead Sponsor: Mayo Clinic

Brief Summary

This clinical trial studies the utilization of glutamine by the bone marrow plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS) compared to multiple myeloma (MM). Results from this study may identify metabolic differences between pre-malignant and malignant clonal plasma cells in MGUS and MM, respectively. It may also allow researchers better determine the transition from MGUS to MM for the development of potential early diagnostic purposes of preventative strategies.

Detailed Description

PRIMARY OBJECTIVE:

I. Compare the glutamine anaplerosis activity in bone marrow clonal plasma cells (cPCs) between patients with MGUS and MM using an in vivo and an ex vivo approach.

SECONDARY OBJECTIVES:

I. Compare the tricarboxylic acid (TCA) isotopomer enrichment in the bone marrow plasma obtained from patients with MGUS and MM with the in vivo approach.

II. Determine the peripheral blood enrichment of 13C in the TCA cycle intermediates from patients with MGUS and MM with the in vivo approach.

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP I (EX-VIVO): After an overnight fast of 6 hours, patients undergo collection of blood samples.

GROUP II (IN VIVO): After an overnight fast of 6 hours, patients receive 13-carbon labeled glutamine or 13-carbon-labeled glucose intravenously (IV) over 90 minutes. Patients also undergo collection of blood and bone marrow aspirate samples.

After completion of study, patient are followed up for 4 weeks.

Study Timeline

• Study First Submitted: 2017-04-12
• Study First Submitted QC: 2017-04-14
• Study First Posted: 2017-04-19
• Study Start: 2017-06-02
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-07
• Last Update Posted: 2024-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 35

Inclusion Criteria

• At least 18 years of age
• International Myeloma Working Group (IMWG) criteria for the diagnosis of either MGUS or MM

Exclusion Criteria

• Unable to provide consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) > 3
• Hemoglobin < 8 g/dL
• Women who are pregnant
• Prior history of adverse events with conscious sedation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group II (biospecimen collection, glutamine, glucose)	Biospecimen Collection	IN VIVO: After an overnight fast of 6 hours, patients receive 13-carbon labeled glutamine or 13-carbon-labeled glucose IV over 90 minutes. Patients also undergo collection of blood and bone marrow aspirate samples.
Group II (biospecimen collection, glutamine, glucose)	5-Carbon C 13-labeled Glutamine	IN VIVO: After an overnight fast of 6 hours, patients receive 13-carbon labeled glutamine or 13-carbon-labeled glucose IV over 90 minutes. Patients also undergo collection of blood and bone marrow aspirate samples.
Group I (biospecimen collection)	Biospecimen Collection	EX-VIVO: After an overnight fast of 6 hours, patients undergo collection of bone marrow aspirate samples.
Group II (biospecimen collection, glutamine, glucose)	Uniformly-labeled [13C]glucose	IN VIVO: After an overnight fast of 6 hours, patients receive 13-carbon labeled glutamine or 13-carbon-labeled glucose IV over 90 minutes. Patients also undergo collection of blood and bone marrow aspirate samples.

Primary Outcome Measures

Name	Time	Method
Percent enrichment of 13-Carbon in the tricarboxylic acid (TCA) cycle intermediates within bone marrow plasma cells from patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma	Up to 1 day	Will compare the glutamine anaplerosis activity in bone marrow clonal plasma cells between patients with MGUS and multiple myeloma.

Secondary Outcome Measures

Name	Time	Method
Percent enrichment of 13-Carbon in the TCA cycle intermediates within the peripheral blood plasma from patients with MGUS and multiple myeloma	Up to 1 day	Will compare the peripheral blood enrichment of 13-carbon in the TCA cycle intermediates from patients with MGUS and multiple myeloma.
Percent enrichment of 13-Carbon in the TCA cycle intermediates within bone marrow plasma from patients with MGUS and multiple myeloma	Up to 1 day	Will compare the glutamine anaplerosis activity in the plasma cells by assessing the bone marrow plasma between patients with MGUS and multiple myeloma.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States