Exercise for Blood Cancer

(Allo-X Trial)

Overseen By Forrest L Baker, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Arizona

Must not be taking: Antidepressants, Immune modulators, others

Disqualifiers: Tobacco use, High BMI, Cardiovascular disease, Autoimmune disease, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 13

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that affect the immune system, ibuprofen/aspirin, antidepressants, or medications that alter blood pressure or cardiovascular function, as well as any prescription medications or beta-blockers.

What data supports the effectiveness of the treatment Exercise, Physical Activity, Workout, Fitness Training for blood cancer?

Research suggests that exercise can improve physical fitness, reduce fatigue, and enhance quality of life in patients with blood cancer, especially those undergoing stem cell transplantation. Although more research is needed, exercise appears to be safe and beneficial for these patients. ^{1 2 3 4 5}

Is exercise safe for people with blood cancer?

Exercise is generally considered safe for people with blood cancer, even during chemotherapy. Studies suggest it can help improve physical and mental well-being, though more research is needed to determine the best type and amount of exercise for these patients. ^{1 2 6 7 8}

How does the treatment of exercise differ from other treatments for blood cancer?

Exercise is unique for blood cancer treatment as it focuses on improving physical and psychological well-being, potentially enhancing immune function, rather than directly targeting cancer cells like traditional treatments. It is a non-invasive approach that can alleviate treatment-related symptoms and improve quality of life, though specific guidelines for its use in blood cancer are still being researched. ^{1 2 6 8 9}

What is the purpose of this trial?

This study aims to improve the treatment of blood cancer by using exercise to collect healthier immune cells from donors. Allogeneic adoptive cell therapy is a treatment where immune cells from a healthy donor are given to a cancer patient, usually to help prevent or treat cancer relapse after a stem cell transplant. These donor cells can either be directly infused into the patient or grown in a lab to create more specialized immune cells that target and kill cancer. While this therapy has been helpful for many patients, there is a need to make it more effective for a larger group and reduce side effects like graft-versus-host disease (GvHD), where the donor's immune cells attack the patient's healthy tissue. This Early Phase 1 trial will test whether exercise can help produce better immune cells from donors. The investigators will recruit healthy participants for three study groups: 1. Exercise Group: Participants will complete a 20-minute cycling exercise session. The investigators will collect blood samples before, during, and after exercise to study the number and quality of immune cells. The investigators will also use the collected cells to create immune therapies and test their ability to kill cancer cells in the lab and control cancer growth in mice. 2. Exercise and Beta Blocker Group: In this group, participants will complete up to five cycling sessions, with at least a week between each session. Before each session, participants will take either a placebo or a drug (beta blocker) that blocks stress hormones like adrenaline. The investigators will collect blood samples before and during exercise to see how blocking these hormones changes the effect of exercise on immune cells. 3. Isoproterenol Group: Participants in this group will receive a 20-minute infusion of isoproterenol, a drug that mimics the effects of adrenaline. The investigators will collect blood samples before, during, and after the infusion to see if the drug causes similar immune changes to those caused by exercise. Participants can join one, two, or all three groups. This research will help understand whether exercise can improve immune cell therapies for treating blood cancer and reduce the risk of GvHD, making these treatments safer and more effective.

Eligibility Criteria

This trial is for healthy individuals who can donate immune cells to help improve blood cancer treatments. It's not specified, but typically participants should be adults, in good health, and able to perform exercise or take medications as required by the study.

Inclusion Criteria

Participants must be classified as 'low-risk' for graded exercise/stress testing according to ACSM-AHA criteria

I can safely use certain heart and lung medications as per FDA guidelines.

I am between 21 and 55 years old.

Exclusion Criteria

I have heart issues or can't take certain heart medications.

I am currently using tobacco or quit less than 6 months ago.

I have had a common illness, like a cold, in the last 6 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Exercise Cohort

Participants undergo a graded exercise test and two exercise sessions to collect blood samples for immune cell analysis.

3-4 weeks

3 visits (in-person)

Exercise + Beta Blocker Cohort

Participants complete five exercise trials with drug or placebo administration to study the effects on immune cells.

6-10 weeks

6 visits (in-person)

Isoproterenol Cohort

Participants receive isoproterenol infusion to mimic exercise effects on immune cells.

2-3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after interventions.

4 weeks

Treatment Details

Interventions

• Exercise

Trial Overview The trial tests if exercise or certain drugs (beta blockers and isoproterenol) can produce healthier immune cells from donors for cell therapies used in treating blood cancers like lymphoma and leukemia. The study has three groups: one exercising, one taking beta blockers with exercise, and one receiving a drug mimicking adrenaline effects.

Participant Groups

Group I: Isoproterenol Infusion Cohort Experimental Treatment 1 Intervention

To determine if pharmacological activation of beta-adrenergic receptors evokes an immune respponse akin to exercise, healthy participants will receive an intravenous infusion of isoproterenol (50ng/kg/min)

Group II: Exercise Cohort Experimental Treatment 1 Intervention

After an initial maximal graded exercise test to determine maximal oxygen uptake and peak cycling power, healthy participants will undergo a 20-minute graded exercise test at intensities corresponding to 50, 60, 70 and 80% VO2max (5-minutes per stage)

Group III: Exercise + Beta Blocker Cohort Placebo Group 5 Interventions

Healthy participants will complete a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake under the following conditions: (1) Placebo; (2) 10mg bisoprolol ingestion; (3) 80ng nadolol ingestion; (4) 50ng carvedilol ingestion; (5) 10mg bisoprolol + 100mcg roflumilast ingestion. All drugs and placebo will be ingested 2-3h prior to exercise. Trial conditions will be double-blind and cross over with each participant serving as their own cntrol

Who Is Running the Clinical Trial?

University of Arizona

Lead Sponsor

Trials

545

Recruited

161,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Patients with hematologic malignancies often experience significant physical and cognitive challenges, highlighting the need for early and comprehensive rehabilitation services, including exercise interventions.

Current research suggests that exercise is generally safe and can lead to functional improvements for patients with hematologic cancers, but more studies are needed to establish effective guidelines, especially for those undergoing stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation and exercise considerations in hematologic malignancies. Paul, KL.[2016]

Exercise has been shown to significantly improve physical and psychological well-being in cancer patients, particularly in reducing fatigue, depression, and anxiety, as well as enhancing fitness levels during and after cancer treatment.

While exercise is feasible for patients with hematological cancers and may help alleviate treatment-related symptoms, more research is needed to determine the most effective exercise protocols for this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical activity and hematological cancer survivorship. Battaglini, CL.[2015]

Exercise interventions significantly improve lower muscle strength, fatigue, and quality of life in patients undergoing hematopoietic stem cell transplantation, based on a meta-analysis of randomized controlled trials.

Starting exercise before transplantation is optimal for enhancing muscle strength and quality of life, with no increase in adverse events such as graft vs host disease or mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise for physical fitness, fatigue and quality of life of patients undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials. Liang, Y., Zhou, M., Wang, F., et al.[2022]

A systematic review of 8 studies found that exercise interventions significantly improve cardiorespiratory fitness and lower extremity muscle strength in patients with hematologic malignancies undergoing stem cell transplantation, with effect sizes of 0.53 and 0.56, respectively.

Exercise also helps reduce fatigue and positively impacts overall quality of life, although all studies had some risk of bias, indicating a need for further high-quality research to confirm these benefits and optimize exercise interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise in patients treated with stem cell transplantation for a hematologic malignancy: a systematic review and meta-analysis. Persoon, S., Kersten, MJ., van der Weiden, K., et al.[2022]

A systematic review of 15 studies found that exercise interventions significantly improved physical fitness in adults with hematological malignancies, as measured by the 6-minute walk test and peak oxygen consumption.

While exercise did not show significant effects on grip strength, fatigue, or overall quality of life when comparing groups, within-group analysis indicated that combination exercise improved quality of life for participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise interventions for physical fitness, fatigue, and quality of life in adult hematologic malignancy patients without receiving hematopoietic stem cell transplantation: a systematic review and meta-analysis. Xu, W., Yang, L., Wang, Y., et al.[2022]

Exercise interventions during and after chemotherapy for patients with hematological cancer are generally reported as safe and feasible, based on a systematic review of 12 studies, including six randomized controlled trials.

Despite the positive claims about safety and feasibility, many studies lack detailed information on how these conclusions were reached, highlighting the need for more comprehensive reporting in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of exercise interventions in patients with hematological cancer undergoing chemotherapy: a systematic review. Großek, A., Großek, K., Bloch, W.[2023]

Exercise therapy significantly improves cardiorespiratory fitness (CRF) in patients with adult-onset cancer, with an average increase of 2.80 mL O2 × kg-1 × min-1 compared to no change in control groups, based on a review of 48 randomized controlled trials involving 3,632 patients.

The study found that exercise therapy is safe, with only 44 adverse events reported across 30 trials, and high adherence rates (88%) suggest that patients are likely to stick with the program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Exercise Therapy on Cardiorespiratory Fitness in Patients With Cancer: A Systematic Review and Meta-Analysis. Scott, JM., Zabor, EC., Schwitzer, E., et al.[2022]

A 12-week exercise rehabilitation program significantly improved cancer-related fatigue, cardiovascular fitness, quality of life, muscle strength, and body composition in hematological cancer patients, with no adverse reactions reported.

Patients who initially received usual care showed similar significant improvements after participating in a delayed exercise program, indicating the lasting benefits of exercise rehabilitation for cancer recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised controlled trial comparing the effects of a 12-week supervised exercise versus usual care on outcomes in haematological cancer patients. Furzer, BJ., Ackland, TR., Wallman, KE., et al.[2019]

Exercise is increasingly recognized as beneficial for cancer care, particularly in improving immune function in patients with hematologic cancers, although the exact biological mechanisms are not fully understood.

A review of 7 studies indicates that exercise positively influences various immune cells and cytokines, suggesting that physical activity may enhance the immune environment in patients with hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of exercise on the immune system and outcomes in hematologic malignancies. Sitlinger, A., Brander, DM., Bartlett, DB.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Rehabilitation and exercise considerations in hematologic malignancies. [2016]

2. Germany pubmed.ncbi.nlm.nih.gov

Physical activity and hematological cancer survivorship. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Exercise for physical fitness, fatigue and quality of life of patients undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of exercise in patients treated with stem cell transplantation for a hematologic malignancy: a systematic review and meta-analysis. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Effects of exercise interventions for physical fitness, fatigue, and quality of life in adult hematologic malignancy patients without receiving hematopoietic stem cell transplantation: a systematic review and meta-analysis. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety and feasibility of exercise interventions in patients with hematological cancer undergoing chemotherapy: a systematic review. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Exercise Therapy on Cardiorespiratory Fitness in Patients With Cancer: A Systematic Review and Meta-Analysis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

A randomised controlled trial comparing the effects of a 12-week supervised exercise versus usual care on outcomes in haematological cancer patients. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Impact of exercise on the immune system and outcomes in hematologic malignancies. [2021]