NCT06643221 · University of Arizona
Exercise as an Immune Adjuvant for Allogeneic Cell Therapies
(Allo-X)
What this study is about
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.
View original scientific description
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.
Interventions
BEHAVIORAL
Exercise
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)
DRUG
Isoproterenol
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)
DRUG
Placebo
Healthy participants will consume the placebo 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake
DRUG
Bisoprolol Fumarate Tablet 10 mg
Healthy participants will consume a 10mg Bisoprolol Fumerate tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake
DRUG
Nadolol (1 x 80 mg) Tablets (Invamed, Inc)
Healthy participants will consume a 80mg Nadolol tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake
DRUG
Carvedilol 50 mg
Healthy participants will consume a 50mg Carvedilol tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake
DRUG
Roflumilast 500 Mcg Oral Tablet
Healthy participants will consume a 500mcg Roflumilast tablet and a 10mg Bisoprolol tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake
Primary outcome measures
Immune Cell Enumeration and Phenotyping
Time frame: immediately after the intervention
Whole blood samples will be analyzed for complete blood counts and to quantify lymphocyte and monocyte subtypes using flow cytometry and a comprehensive immunophenotyping panel. This panel is designed to identify major immune cell populations, as well as markers related to differentiation, exhaustion, migration, activation, and inhibition. Specific cell types expressing a surface protein, or combinations of surface proteins, will be reported as the percentage of cells positive for expression and/or by mean fluorescent intensity (MFI). For descriptive purposes, the cell counts of all major lymphocyte and monocyte subtypes will be expressed as cells per microliter (cells/µL) of whole blood. Additionally, isolated peripheral blood mononuclear cells (PBMCs) and expanded cell products will be quantified and phenotyped in a similar manner.
Cytolysis in vitro
Time frame: immediately after the intervention
We will assess whether lymphocytes collected during or after exercise, as well as cell products manufactured from these lymphocytes, are more effective at killing hematologic cancer target cells. Using in vitro assays, such as flow cytometry and bioluminescence-based assays, we will compare the cytolytic activity of both the collected lymphocytes and the manufactured cell products to those obtained under resting conditions. Results will be measured as the time required to achieve 10%, 20%, 30%, 40%, and 50% cytolysis, or as the percentage of target cells killed at specific time points (e.g., 4, 8, 24, and 48 hours). We will also evaluate the impact of combination therapies, such as monoclonal antibodies targeting the tumor model, as appropriate.
Tumor Burden and Tumor Free Survival
Time frame: up to 120-days
Tumor burden will be evaluated in immunocompromised mice engrafted with human tumors by measuring the size, number, and progression of tumors using imaging techniques such as bioluminescence, MRI, or CT scans, along with physical measurements where applicable. Overall tumor burden will be assessed through metrics like peak tumor size and photon intensity in bioluminescence imaging. Tumor-free survival will be defined as the time from treatment until either the recurrence of detectable tumors or the last follow-up without tumor recurrence. Data will be reported as overall tumor reduction (e.g., percentage decrease in tumor size or number), peak tumor burden, and photon intensity, as well as the duration of tumor-free survival in days. Additional analyses will explore the effects of treatment on delaying tumor progression and improving overall survival.
Clinical xGvHD Score
Time frame: up to 120-days
The development of xGvHD (xenogeneic graft-versus-host disease) will be assessed using a clinical scoring system with a possible aggregate score ranging from 0 to 10. Animals will be monitored regularly, and a total score of 5 or higher on two consecutive assessment days will indicate the presence of moderate xGvHD. This scoring system allows for the systematic evaluation of disease severity and progression in response to treatment.
Survival
Time frame: up to 120 days
Survival will be monitored as a critical endpoint in this study. Death will be recorded when any of the following criteria are met: (1) the animal experiences greater than 20% weight loss compared to its baseline weight at two consecutive weigh-ins, indicating significant deterioration in health; or (2) the animal exhibits signs of severe morbidity, characterized by an xGvHD score exceeding 7. These criteria ensure that any adverse effects related to treatment or disease progression are accurately captured, allowing for a comprehensive assessment of the survival outcomes in the context of xGvHD.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Participants must:
- Be between 21 and 55 years of age.
- Be classified as 'low-risk' for graded exercise/stress testing according to ACSM-AHA criteria.
- Have no contraindications for the use of isoproterenol, carvedilol, bisoprolol, nadolol, or roflumilast as per FDA guidelines.
Exclusion criteria
- Participants will be excluded if they:
- Currently use tobacco products or have quit within the last 6 months.
- Have a body mass index (BMI) greater than 34 kg/m² or waist circumference exceeding 102 cm for men and 88 cm for women.
- Use any medications known to affect the immune system or regularly take ibuprofen/aspirin, antidepressants, or medications that alter blood pressure or cardiovascular function.
- Use of hormone replacement therapy.
- Are pregnant or breastfeeding.
- Have chronic or debilitating arthritis or have been bedridden in the past three months.
- Experienced a common illness (e.g., colds) within the past 6 weeks.
- Have central or peripheral nervous disorders, a history of stroke, or major affective disorder.
- Are infected with HIV or hepatitis or have any autoimmune disease.
- Have known cardiovascular disease or contraindications for the use of isoproterenol, carvedilol, bisoprolol, nadolol, or roflumilast.
- Use any prescription medications or have an allergy to beta-blockers.
- Have a resting heart rate of less than 50 beats per minute.
- Suffer from asthma, emphysema, bronchitis, kidney disease, pheochromocytoma, diabetes, overactive thyroid, or a history of severe anaphylactic reactions.
- Are scheduled for surgery. Additionally, participants who meet the inclusion criteria but present with more than one of the following cardiovascular disease (CVD) risk factors will be excluded unless cleared by a cardiologist:
- Family History: Myocardial infarction, coronary revascularization, or sudden death before 55 years of age in a father or male first-degree relative, or before 65 years of age in a mother or female first-degree relative.
- Hypertension: Systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg.
- Dyslipidemia: Total serum cholesterol exceeding 200 mg/dl.
- Pre-diabetes: Fasting blood glucose levels between 100 mg/dl and 126 mg/dl.
Where
- Tucson, Arizona
Collaborators
National Cancer Institute (NCI)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 5, 2026 · Source of record for eligibility and locations