The Effects of Exercise on Immune Phenotype of Indolent Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia Patients

The Effects of Acute and Chronic Exercise on the Immune Phenotype of Indolent Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia Patients

This clinical trial studies the effect of short-term (acute) and long-term (chronic) exercise on immune characteristics and function (phenotype) of patients with indolent non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Most newly-diagnosed CLL patients have early-stage disease at the time of diagnosis and do not require treatment. Despite not needing therapy, these patients have significant immune dysfunction. This may lead to an increased risk of serious infections requiring hospitalization and an increased risk of secondary non-blood-based (hematologic) cancers. Increasing CLL patients overall physical fitness levels, through exercise during the observation stage, may provide a realistic approach means to increase survival, decrease treatment-related side effects, and improve immune function. Information learned from this study may help researchers determine whether a particular exercise regimen can be used to strengthen the immune system of indolent NHL and CLL patients, delay time to disease progression, assess the need for treatment, and assess infection rates.

Study Overview

• Status: Recruiting
• Conditions: Indolent Non-hodgkin Lymphoma; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Intervention / Treatment: Other: Questionnaire Administration; Other: Best Practice; Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Procedure: Dual X-ray Absorptiometry; Other: Cardiopulmonary Exercise Testing; Procedure: Spirometry; Procedure: Physical Examination; Other: Exercise Intervention; Other: Physical Performance Testing

Detailed Description

PRIMARY OBJECTIVES:

I. Determine how circulating immune cell abundance and function (via cell counts & cytokine profile) of CLL patients respond to acute (single bout) maximal exercise and how this differs from the response observed in group of age-matched controls by monitoring cardiopulmonary parameters and mobilization of immune cell phenotypes.

II. Determine how circulating immune cell mobilization and function (cell counts & cytokine profile) of CLL patients respond to a 12-week semi-supervised training program of moderate to high intensity, aerobic based exercise.

III. Evaluate the effectiveness of 12-weeks of semi-supervised exercise training (ET) versus (vs.) usual care (UC) at reducing cancer-related side effects and improving quality of life (QOL) and physical fitness in individuals with indolent non-Hodgkin (NHL) lymphoma during or after treatment.

IV. Determine that extent to which 12-weeks of semi-supervised ET can modify circulating immune cell mobilization and immune function in individuals with indolent NHL during or after treatment compared to UC.

V. Development of a forward-chaining AI expert system using both manual and physiology derived feedback to optimize training results and compare its efficacy at reducing cancer-related side effects and improving quality of life (QOL) and physical fitness in individuals with indolent NHL and CLL to that of the semi-supervised ET.

OUTLINE: CLL patients and healthy participants are assigned to Aim 1. CLL patients who complete all Aim 1 activities are assigned to Aim 2. Patients with indolent NHL will be assigned to Aims 3 and 4.

AIM 1: Participants undergo measurement of height/weight and vital signs (blood pressure, temperature, heart and breathing rate), complete lung function testing (spirometry), undergo an exercise test (cardiopulmonary exercise testing [CPET]), and undergo collection of blood samples on study. Participants may also undergo dual X-ray absorptiometry (DEXA) scan on study.

AIM 2: CLL patients complete aerobic based training program on study. Patients then complete all Aim 1 activities again after completion of aerobic based training program.

AIMS 3-4: Indolent NHL patients undergo measurement of height/weight and vital signs (blood pressure, temperature, heart and breathing rate), complete lung function testing (spirometry), undergo an exercise test (CPET), and undergo collection of blood samples on study. Participants may also undergo DEXA scan on study. Patients undergo muscular strength and functional endurance measurements of hand grip strength, upper body power via weighted chest pass, and leg strength with the timed chair stand test and 6-minute walk test (6MWT). Patients are then randomized to 1 of 2 arms.

ARM I: Patients receive usual care on study.

ARM II: Patients complete aerobic based training program on study. Patients then complete all baseline activities again after completion of aerobic based training program.

AIM 5: All patients from Aims 3-4 will be invited to repeat Aims 3-4 baseline activities.

After completion of study intervention, patients are followed up every 6 months (Aims 2-4) or annually (Aim 5) for 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
• Study Contact Backup: Name: Courtney Wheatley-Guy, PhD; Phone Number: 480-301-8976; Email: wheatley.courtney@mayo.edu

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic in Arizona
      • Contact: Jordan Parks; Phone Number: 480-301-6616; Email: parks.jordan@mayo.edu
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Michael P. Gustafson, PhD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Rochester
      • Contact: Briana Ziegler; Phone Number: 507-255-7125; Email: zeigler.briana@mayo.edu
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Principal Investigator: Neil E. Kay, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• English speaking
• Between the ages of 18-80
• Histologically confirmed diagnosis of indolent non-Hodgkin lymphoma (NHL) will be required to participate in Aim 2 (CLL/SLL only), aim 3 and 4 (indolent NHL) and aim 5 (indolent NHL) of this study

Exclusion Criteria:

• Healthy subjects participating in Aim 1 will be excluded if they have known cardiovascular or pulmonary disease (e.g. heart disease, coronary artery disease, chronic obstructive pulmonary disease [COPD], asthma, etc.) an orthopedic or musculoskeletal limitation which would limit ability to exercise or are a current or former smoker
• Indolent NHL individuals receiving treatment must have least 8 weeks of planned treatment remaining and those who have already received treatment must be at least 6 months post and have no planned treatments during the 12-week intervention period to be eligible. Individuals that are participating prior to receiving treatment must not have any scheduled treatments during their participation. Individuals will be excluded if they have uncontrolled hypertension, cardiac illness, or are not approved by their oncologist to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aim 1 (vitals, spirometry, CPET, blood samples, DEXA); Participants undergo measurement of height/weight and vital signs (blood pressure, temperature, heart and breathing rate), complete lung function testing (spirometry), undergo an exercise test (CPET), and undergo collection of blood samples on study. Participants may also undergo DEXA scan on study.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: Electronic Health Record Review; Ancillary studies; Procedure: Dual X-ray Absorptiometry; Undergo DEXA scan; Other Names: DEXA; DXA; BMD scan; bone mineral density scan; DEXA Scan; dual energy x-ray absorptiometric scan; Dual Energy X-ray Absorptiometry; Dual X-Ray Absorptometry; DXA SCAN; DEXA (Bone Density); Other: Cardiopulmonary Exercise Testing; Undergo CPET; Other Names: CPET; CPX; Procedure: Spirometry; Undergo spirometry; Procedure: Physical Examination; Undergo measurement of height/weight and vital signs; Other Names: Assessment; General Examination; Physical; Physical Assessment; Physical Exam; physical_exam; Physical examination procedure (procedure)
Experimental: Aim 2 (aerobic based training program, Aim 1 activities); CLL patients complete aerobic based training program on study. Patients then complete all Aim 1 activities again after completion of aerobic based training program.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: Electronic Health Record Review; Ancillary studies; Procedure: Dual X-ray Absorptiometry; Undergo DEXA scan; Other Names: DEXA; DXA; BMD scan; bone mineral density scan; DEXA Scan; dual energy x-ray absorptiometric scan; Dual Energy X-ray Absorptiometry; Dual X-Ray Absorptometry; DXA SCAN; DEXA (Bone Density); Other: Cardiopulmonary Exercise Testing; Undergo CPET; Other Names: CPET; CPX; Procedure: Spirometry; Undergo spirometry; Procedure: Physical Examination; Undergo measurement of height/weight and vital signs; Other Names: Assessment; General Examination; Physical; Physical Assessment; Physical Exam; physical_exam; Physical examination procedure (procedure); Other: Exercise Intervention; Undergo aerobic based training program
Active Comparator: Aims 3-4 arm I (indolent NHL usual care); Indolent NHL patients undergo measurement of height/weight and vital signs (blood pressure, temperature, heart and breathing rate), complete lung function testing (spirometry), undergo an exercise test (CPET), and undergo collection of blood samples on study. Participants may also undergo DEXA scan on study. Patients undergo muscular strength and functional endurance measurements of hand grip strength, upper body power via weighted chest pass, and leg strength with the timed chair stand test and 6MWT. Patients receive usual care on study.	Other: Questionnaire Administration; Ancillary studies; Other: Best Practice; Receive usual care; Other Names: standard of care; standard therapy; Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: Electronic Health Record Review; Ancillary studies; Procedure: Dual X-ray Absorptiometry; Undergo DEXA scan; Other Names: DEXA; DXA; BMD scan; bone mineral density scan; DEXA Scan; dual energy x-ray absorptiometric scan; Dual Energy X-ray Absorptiometry; Dual X-Ray Absorptometry; DXA SCAN; DEXA (Bone Density); Other: Cardiopulmonary Exercise Testing; Undergo CPET; Other Names: CPET; CPX; Procedure: Spirometry; Undergo spirometry; Procedure: Physical Examination; Undergo measurement of height/weight and vital signs; Other Names: Assessment; General Examination; Physical; Physical Assessment; Physical Exam; physical_exam; Physical examination procedure (procedure); Other: Physical Performance Testing; Undergo muscular strength and functional endurance measurements; Other Names: Physical Fitness Testing; Physical Function Testing
Active Comparator: Aims 3-4 arm II (indolent NHL aerobic based training program); Indolent NHL patients undergo measurement of height/weight and vital signs (blood pressure, temperature, heart and breathing rate), complete lung function testing (spirometry), undergo an exercise test (CPET), and undergo collection of blood samples on study. Participants may also undergo DEXA scan on study. Patients undergo muscular strength and functional endurance measurements of hand grip strength, upper body power via weighted chest pass, and leg strength with the timed chair stand test and 6MWT. Patients complete aerobic based training program on study. Patients then complete all baseline activities again after completion of aerobic based training program.	Other: Questionnaire Administration; Ancillary studies; Other: Best Practice; Receive usual care; Other Names: standard of care; standard therapy; Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: Electronic Health Record Review; Ancillary studies; Procedure: Dual X-ray Absorptiometry; Undergo DEXA scan; Other Names: DEXA; DXA; BMD scan; bone mineral density scan; DEXA Scan; dual energy x-ray absorptiometric scan; Dual Energy X-ray Absorptiometry; Dual X-Ray Absorptometry; DXA SCAN; DEXA (Bone Density); Other: Cardiopulmonary Exercise Testing; Undergo CPET; Other Names: CPET; CPX; Procedure: Spirometry; Undergo spirometry; Procedure: Physical Examination; Undergo measurement of height/weight and vital signs; Other Names: Assessment; General Examination; Physical; Physical Assessment; Physical Exam; physical_exam; Physical examination procedure (procedure); Other: Exercise Intervention; Undergo aerobic based training program; Other: Physical Performance Testing; Undergo muscular strength and functional endurance measurements; Other Names: Physical Fitness Testing; Physical Function Testing
Experimental: Aim 5 (repeat baseline activities); All patients from Aims 3-4 will be invited to repeat Aims 3-4 baseline activities.	Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo collection of blood; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: Electronic Health Record Review; Ancillary studies; Procedure: Dual X-ray Absorptiometry; Undergo DEXA scan; Other Names: DEXA; DXA; BMD scan; bone mineral density scan; DEXA Scan; dual energy x-ray absorptiometric scan; Dual Energy X-ray Absorptiometry; Dual X-Ray Absorptometry; DXA SCAN; DEXA (Bone Density); Other: Cardiopulmonary Exercise Testing; Undergo CPET; Other Names: CPET; CPX; Procedure: Spirometry; Undergo spirometry; Procedure: Physical Examination; Undergo measurement of height/weight and vital signs; Other Names: Assessment; General Examination; Physical; Physical Assessment; Physical Exam; physical_exam; Physical examination procedure (procedure); Other: Physical Performance Testing; Undergo muscular strength and functional endurance measurements; Other Names: Physical Fitness Testing; Physical Function Testing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess circulating immune cell abundance and function pre-intervention	A standardized questionnaire will be administered to assess levels of past and current physical activity. Baseline measurement of pulmonary function (PFT) will be collected and possibly a body composition scan via dual x-ray absorptiometry (DEXA). While subjects perform cardiopulmonary exercise testing (CPET), cardiopulmonary vitals will be assessed and monitored throughout exercise and in recovery. A 40 mL venous blood sample will be drawn at baseline and post exercise (80 mL total), along with finger prick measures of blood lactate at rest and early recovery. Blood samples will be evaluated to determine how circulating immune cell abundance and function (via cell counts & cytokine profile) of chronic lymphocytic leukemia (CLL) patients respond to acute (single bout) maximal exercise and how this differs from the response observed in group of age-matched controls by monitoring cardiopulmonary parameters and mobilization of immune cell phenotypes.	Baseline
Assess circulating immune cell mobilization and function post-intervention	Each subject will participate in a 12-weeks exercise program (3 times per week) at a moderate to high exercise intensity level based upon the results of their cardiopulmonary exercise testing (CPET)]. Upon completion of the program, subjects will return to the laboratory for post testing using the same techniques as used during the baseline. Venous blood samples drawn at rest after the program will be used to determine how circulating immune cell mobilization and function (cell counts and cytokine profile) of CLL patients respond to intervention. Usual descriptive statistics will be performed - means, standard deviations, and ranges. Comparisons within a group over time or pre/post will be performed using paired t-tests, while comparisons between groups will be performed using unpaired t-tests or where necessary using ANOVA. Comparisons will be made based on absolute values as well as changes during a test.	Up to 12 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael P. Gustafson, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2023
• Primary Completion (Estimated): March 13, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Lymphocytic, Chronic, B-Cell; Health Services Administration; Health Care Quality, Access, and Evaluation; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Quality of Health Care; Quality Indicators, Health Care; Diagnostic Imaging; Chemistry Techniques, Analytical; Diagnostic Techniques, Respiratory System; Diagnostic Techniques, Cardiovascular; Behavior Control; Immobilization; Guidelines as Topic; Quality Assurance, Health Care; Radiography; Heart Function Tests; Respiratory Function Tests; Ergometry; Densitometry; Photometry; Standard of Care; Specimen Handling; Restraint, Physical; Practice Guidelines as Topic; Exercise Test; Absorptiometry, Photon; Bone Density; Clostridium perfringens epsilon-toxin
• Other Study ID Numbers: 22-012246 (Other Identifier: Mayo Clinic Institutional Review Board); NCI-2023-03210 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No