Dysregulation of Glutamine Activity in the Pathogenesis of Multiple Myeloma

Mayo Clinic

Status: Completed

Conditions: Plasma Cell Myeloma; Monoclonal Gammopathy of Undetermined Significance

Treatments: Other: Uniformly-labeled [13C]glucose; Procedure: Biospecimen Collection; Other: 5-Carbon C 13-labeled Glutamine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03119883

K23CA218742 (U.S. NIH Grant/Contract)

NCI-2021-02642 (Registry Identifier)

17-003133

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 2 patient groups

Group I (biospecimen collection)

Experimental group

Description:

EX-VIVO: After an overnight fast of 6 hours, patients undergo collection of bone marrow aspirate samples.

Treatment:

Procedure: Biospecimen Collection

Procedure: Biospecimen Collection

Group II (biospecimen collection, glutamine, glucose)

Experimental group

Description:

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.

Treatment:

Other: 5-Carbon C 13-labeled Glutamine

Procedure: Biospecimen Collection

Procedure: Biospecimen Collection

Other: Uniformly-labeled [13C]glucose