In Vivo Metabolic Profiling of CLL (Chronic Lymphocytic Leukemia)

NCT ID: NCT04785989

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 16 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-13
• Study Completion Date: 2026-10-31

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Group A: Healthy volunteers

Healthy volunteers are defined as people without a history of cancer

[U-13C]glucose

Intervention Type: 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 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.

[13C5]glutamine

Intervention Type: 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-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.

[U-13C]glucose

Intervention Type: 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 C:Treatment naïve CLL patients with high systemic disease burden

Treatment naïve CLL patients with high systemic disease burden

[U-13C]glucose

Intervention Type: 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.

Interventions

[U-13C]glucose

\[U-13C\]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.

Intervention Type: OTHER

[13C5]glutamine

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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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
• Documented Informed Consent

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Fletcher, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

University of Wisconsin

Madison, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Cancer Connect

Role: CONTACT

clinicaltrials@cancer.wisc.edu

800-622-8922

Other Identifiers

MSN240796

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SMPH/MEDICINE/HEM-ONC

Identifier Type: OTHER

Identifier Source: secondary_id

A534260

Identifier Type: OTHER

Identifier Source: secondary_id

Protocol Version 10/19/2022

Identifier Type: OTHER

Identifier Source: secondary_id

2020-1008

Identifier Type: OTHER

Identifier Source: secondary_id

UW20062

Identifier Type: -

Identifier Source: org_study_id