In Vivo Metabolic Profiling of CLL (Chronic Lymphocytic Leukemia)

NCT04785989 | Recruiting DMC

• 6 other identifiers: UW20062MSN240796SMPH/MEDICINE/HEM-ONCA534260Protocol Version 10/19/20222020-1008
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic reprogramming has been identified as a hallmark of cancer. Almost a century after Otto Warburg initially discovered increased glycolytic activity in tumor tissue ("Warburg effect"), therapeutic targeting of cancer metabolism has become a field of intense research effort in cancer biology. A growing appreciation of metabolic heterogeneity and complexity is currently reshaping investigators "simplistic" understanding of metabolic reprogramming in cancer. Discovering metabolic vulnerabilities as new treatment targets for cancer requires systematic dissection of metabolic dependencies, fuel preferences, and underlying mechanisms in the specific physiological context. However, today's data on cancer cell metabolic signatures and heterogeneity in their physiological habitat of the human organism is sparse to non-existent representing a critical knowledge gap in designing effective metabolic therapies. Here, the investigators propose a "top-down" approach studying cancer cell metabolism in patients followed by mechanistic in-depth studies in cell culture and animal models to define metabolic vulnerabilities. Investigators will develop a metabolic tracing method to quantitatively characterize metabolic signatures and fuel preferences of leukemic lymphocytes in patients with chronic lymphocytic leukemia (CLL). Isotopic metabolic tracers are nutrients that are chemically identical to the native nutrient. Incorporated stable, non-radioactive isotopes allow investigators to follow their metabolic fate by monitoring conversion of tracer nutrients into downstream metabolites using cutting-edge metabolomics analysis. Using this method, investigators propose to test the hypothesis that leukemic lymphocytes show tissue-specific metabolic preferences that differ from non-leukemic lymphocytes and that ex vivo in-plasma labeling represents a useful model for assaying metabolic activity in leukemic cells in a patient-specific manner.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Cell metabolic tracing; Leukemic lymphocytes; Fuel preference

Outcome Measures

Primary Outcomes (2)

• Amount of [U-13C]glucose incorporation into metabolites in normal and leukemic lymphocytes: Liquid chromatography-mass spectrometry (LCMS) pharmacokinetic analysis

  It will reveal how CLL cells utilize glucose compared to non-leukemic lymphocytes and how this changes with different disease burden and site of disease. Participants will be on overnight fasting.

  up to 2 hours (± 5 minutes)

• Amount of [U-13C15N]L-glutamine incorporation into metabolites in normal and leukemic lymphocytes: LCMS pharmacokinetic analysis

  It will reveal how CLL cells utilize glutamine compared to non-leukemic lymphocytes and how this changes with different disease burden and site of disease. Participants will be on overnight fasting.

  up to 2 hours (± 5 minutes)

Other Outcomes (1)

• Validate ex vivo labeling model to assay metabolism

  10 minutes

Study Arms (4)

Group A: Healthy volunteers

Healthy volunteers are defined as people without a history of cancer

Other: [U-13C]glucose

Group B subset-1: Treatment naïve CLL(Chronic Lymphocytic Leukemia) patients with low disease burden

Participants with low disease burden CLL (Chronic Lymphocytic Leukemia) defined as confined to Rai stage 0.

Other: [13C5]glutamine

Group B subset-2: Treatment naïve CLL patients with low disease burden

Participants with low disease burden CLL (Chronic Lymphocytic Leukemia) defined as confined to Rai stage 0.

Other: [U-13C]glucose

Group C:Treatment naïve CLL patients with high systemic disease burden

Treatment naïve CLL patients with high systemic disease burden

Other: [U-13C]glucose

Interventions

[U-13C]glucose OTHER

\[U-13C\]glucose will be administered as a bolus of 8 g (grams) over 10 minutes followed by 8 g/hour continuous infusion over 2 hours . This infusion rate will allow glucose tracer to reach sufficient enrichment without causing significant metabolic perturbation such as hyperglycemia.

Group A: Healthy volunteers; Group B subset-2: Treatment naïve CLL patients with low disease burden; Group C:Treatment naïve CLL patients with high systemic disease burden

[13C5]glutamine OTHER

6mg/kg of body weight of \[13C5\]glutamine will be administered as a bolus over 10 minutes (± 1 minute) followed by 6mg/kg/hr body weight continuous infusion for 2 hours through a peripheral IV catheter/line. This infusion rate will allow glutamine tracer to reach sufficient enrichment without causing significant metabolic perturbation such as hyperglycemia.

Group B subset-1: Treatment naïve CLL(Chronic Lymphocytic Leukemia) patients with low disease burden

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

To meet the study aims sixteen (16) adult participants will be enrolled: four (4) healthy volunteers defined as people without a history of cancer, 8 patients with low disease burden CLL (Chronic Lymphocytic Leukemia) defined as confined to Rai stage 0, and 4 patients with high disease burden CLL defined as having extensive infiltration of the bone marrow.

You may qualify if:

• Group A
• Adult (18 years of age or older)
• No previous history of cancer
• Routine history of normal blood counts and vital signs
• Documented Informed Consent
• Group B
• Adult (18 years of age or older)
• Diagnosis of CLL with low disease burden defined as Rai stage 0 ((Lymphocytosis; no enlargement of the lymph nodes, spleen, or liver; red blood cell and platelet counts are near normal.)
• Treatment naïve
• Documented Informed Consent
• Group C
• Adult (18 years of age or older)
• Diagnosis of CLL with high systemic disease burden defined as infiltration of bone marrow causing cytopenia
• Treatment naïve
• Able/willing to have bone marrow aspiration

You may not qualify if:

• For all participants
• Prisoners
• Psychiatric inpatients or people who are institutionalized
• Minor (Less than 18 years of age)
• History of diabetes
• Cannot be on antihyperglycemic therapy
• Carbohydrate restricting diets: Atkins, Vegan, Ketogenic, etc.
• Females of child bearing potential
• Persons without decision-making capacity
• Person who cannot read/write English

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53705, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Christopher Fletcher, MD

  School of Medicine and Public Health, University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 8, 2021
• Study Start: June 13, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)