Exercise as an Immune Adjuvant for Allogeneic Cell Therapies

Conditions

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

Eligibility Criteria

Sex

ALL

Age

21 Years - 55 Years

Healthy Volunteers

Accepted

Interventions

• Exercise — BEHAVIORAL
  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)
• Isoproterenol — DRUG
  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)
• Placebo — DRUG
  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
• Bisoprolol Fumarate Tablet 10 mg — DRUG
  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
• Nadolol (1 x 80 mg) Tablets (Invamed, Inc) — DRUG
  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
• Carvedilol 50 mg — DRUG
  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
• Roflumilast 500 Mcg Oral Tablet — DRUG
  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

Study Details

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.

Key Dates

Start date

Jan 24, 2018

Status verified

Feb 2026

Primary completion

May 31, 2031

Completion

May 31, 2031

Study Design

Enrollment

200 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: Exercise Cohort
  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)
• Placebo Comparator: Exercise + Beta Blocker Cohort
  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
• Experimental: Isoproterenol Infusion Cohort
  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)

Primary Outcome Measure

Immune Cell Enumeration and Phenotyping [ Time Frame: immediately after the intervention ]

Locations (1)

Find similar trials in Tucson, AZ

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