Exercise as an Immune Adjuvant for Allogeneic Cell Therapies

Summary

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.

Conditions

• Leukemia
• Hematopoetic Stem Cell Transplantation
• Donor Lymphocyte Infusion
• CAR T-Cell Therapy
• Lymphoma
• Cell Therapy

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• University of Arizona

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

21 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-01-24

Primary Completion

2028-12-30

Completion

2028-12-30

FDA Drug

Yes

Countries

• United States

Study Locations