Exercise Prehabilitation for Blood Cancers

Overseen By Nathan Parker, PhD, MPH

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Disqualifiers: Unstable cardiac, Pulmonary disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special exercise program can benefit individuals with blood cancers, such as leukemia or lymphoma, as they prepare for CAR-T therapy. CAR-T therapy, a type of immunotherapy, uses modified T-cells to combat cancer. Participants will engage in resistance and aerobic exercises, like brisk walking, to build strength and endurance before treatment. The trial suits those with blood cancers who are not currently doing regular resistance training and plan to undergo CAR-T therapy in about a month. As an unphased trial, this study offers a unique opportunity to enhance treatment preparation and potentially improve outcomes.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this exercise program is safe for individuals preparing for CAR T-cell immunotherapy?

Previous studies have shown that aerobic and resistance exercises are generally safe for people with blood cancers. Aerobic exercise, such as walking or using a stationary bike, can be safely performed right after high-dose chemotherapy and helps prevent loss of physical ability. Resistance training, including exercises like weight lifting, is also safe and feasible for these patients. Even those with low blood counts can usually perform these exercises without major issues.

Chimeric Antigen Receptor (CAR) T-cell therapy is another part of this trial and has been successfully used to treat blood cancers. Although some patients experience side effects, CAR T-cell therapy is often considered safe enough to be a common treatment option. Side effects can include fevers and tiredness. Overall, past studies have shown that the treatments in this trial—exercise and CAR T-cell therapy—are safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for blood cancers, which often focus solely on targeting cancer cells with chemotherapy or radiation, this trial explores the potential benefits of exercise prehabilitation in combination with CAR T-cell immunotherapy. The exercise program aims to boost patients' physical fitness before receiving CAR T-cell therapy, potentially enhancing their overall health and improving treatment outcomes. Researchers are excited about this approach because it might improve patients' ability to tolerate intensive treatments, speed up recovery, and even enhance the effectiveness of CAR T-cell therapy by preparing the body to better handle the demands of the treatment.

What evidence suggests that this trial's exercise prehabilitation treatments could be effective for blood cancers?

Research has shown that CAR T-cell therapy, which participants in this trial will receive, has been very successful in treating blood cancers like multiple myeloma and certain B-cell cancers. This therapy modifies T-cells, a type of immune cell, to help them better locate and attack cancer cells. Many patients have experienced complete cancer remission after this treatment. While CAR T-cell therapy is the main focus, participants in this trial will also engage in an exercise prehabilitation program. Studies have found that physical activity, such as strength training and cardio, can improve quality of life and might reduce the chance of cancer recurrence. Although solid proof for exercise alone is limited, it is generally considered beneficial for overall health during cancer treatment. ^{1 3 5 6 7}

Who Is on the Research Team?

Nathan Parker, PhD, MPH

Principal Investigator

Moffitt Cancer Center

Ciara Freeman, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older with leukemia, lymphoma, or myeloma who are set to receive CAR-T cell therapy in at least 4 weeks. They should be relatively active (able to perform daily activities), speak English fluently, and can consent. It's not for those already doing regular resistance training, have exercise safety concerns, severe heart/lung disease, recent serious injuries that affect exercise ability, intense pain, muscle/rheumatic diseases affecting function or major cognitive/sensory issues.

Inclusion Criteria

I am 65 years old or older.

I can take care of myself and am up and about more than half of my waking hours.

I am scheduled for FDA-approved CAR-T therapy in 4 weeks or more.

Exclusion Criteria

Regular engagement in Resistance training (2x/week targeting all major muscle groups)

Screen failure for exercise safety based on Physical Activity Readiness Questionnaire (PAR-Q) and Patient-Reported Measurement Information System (PROMIS) screening questions

Cognitive, visual, or auditory limitations that preclude safe engagement in remotely-supervised resistance training sessions or independent aerobic exercise (as determined by patients' treating oncologists and specified in clinic notes outlining disease history)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Exercise Prehabilitation

Participants engage in an exercise program including resistance training and aerobic exercise for 4-6 weeks prior to CAR-T therapy

4-6 weeks

Approximately 2 visits per week for resistance training

CAR-T Therapy

Participants undergo Chimeric Antigen Receptor (CAR) T-cell immunotherapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after CAR-T therapy

Up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Aerobic Exercise
• Chimeric Antigen Receptor (CAR) T-cell Immunotherapy
• Resistance Training

Trial Overview The study tests an exercise program consisting of resistance and aerobic exercises for older adults preparing for CAR-T cell therapy. The goal is to see if exercising before treatment can help improve outcomes and recovery from the immunotherapy used to treat blood cancers.

How Is the Trial Designed?

Group I: Exercise prehabilitation Experimental Treatment 4 Interventions

Participants will take part in an exercise program in which they will be encouraged to perform approximately 30 minutes of resistance training exercises approximately twice per week until they undergo CAR-T therapy (Approximately 4-6 weeks). Participants will also be encouraged to perform moderate aerobic exercise such as brisk walking or using stationary aerobic equipment at least 3 times per week. Participants will wear a FitBit fitness watch to monitor aerobic exercise.

Chimeric Antigen Receptor (CAR) T-cell Immunotherapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as CAR T-cell therapy for:

• Acute lymphoblastic leukemia (ALL)
• Diffuse large B-cell lymphoma (DLBCL)
• Multiple myeloma
• Follicular lymphoma

Approved in European Union as CAR T-cell therapy for:

• Acute lymphoblastic leukemia (ALL)
• Diffuse large B-cell lymphoma (DLBCL)
• Multiple myeloma
• Follicular lymphoma

Approved in Canada as CAR T-cell therapy for:

• Acute lymphoblastic leukemia (ALL)
• Diffuse large B-cell lymphoma (DLBCL)
• Multiple myeloma

Approved in Japan as CAR T-cell therapy for:

• Acute lymphoblastic leukemia (ALL)
• Diffuse large B-cell lymphoma (DLBCL)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Cancer and Aging Research Group

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

Exercise prehabilitation is crucial for preparing cancer patients for treatments like surgery, with evidence supporting its role in improving fitness and strength, particularly through supervised moderate-intensity aerobic and resistance exercises.

Multimodal prehabilitation programs that include exercise, nutritional support, and psychological interventions are becoming standard practice, enhancing patient outcomes and adherence to treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Exercise Before Cancer Treatment. Denehy, L., Edbrooke, L.[2022]

CAR-T cell therapy shows promise in treating relapsed or refractory malignancies, particularly in hematological cancers like acute B-cell lymphoblastic leukemia and B-cell lymphomas, with ongoing research into its application for solid tumors.

This systematic review aims to comprehensively assess the safety and efficacy of CAR-T cell therapy by analyzing various studies, focusing on outcomes such as complete response rates and adverse events, to better understand its potential risks and benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. Grigor, EJM., Fergusson, DA., Haggar, F., et al.[2019]

CAR T-cell therapy is an innovative treatment for difficult-to-treat blood cancers, but there is limited research on the rehabilitation needs of patients undergoing this therapy.

Patients receiving CAR T-cell therapy often experience cognitive impairments, muscle weakness, and fatigue, suggesting that tailored rehabilitation programs could improve their quality of life and functional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation Needs for Patients Undergoing CAR T-Cell Therapy. Obaisi, O., Fontillas, RC., Patel, K., et al.[2022]

Chimeric antigen receptor (CAR) T-cell therapy has significantly changed the treatment landscape for certain blood cancers, leading to a surge in clinical trials exploring its effectiveness.

The article reviews various clinical trials involving CAR T-cell therapy across both blood cancers and solid tumors, highlighting its potential in a broader range of cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of CAR T-cell clinical trial activity to 2021. Adami, A., Maher, J.[2022]

Adoptive cell therapy using CAR-modified T cells has shown promising results, achieving complete remission in patients with B cell malignancies over the long term.

There are currently around 100 ongoing clinical trials exploring CAR T cell therapies for various blood cancers and solid tumors, highlighting the rapid advancement and interest in this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The growing world of CAR T cell trials: a systematic review. Holzinger, A., Barden, M., Abken, H.[2018]

Exercise and physical activity can enhance immune function in cancer patients, potentially improving their responses to immunotherapies like immune checkpoint inhibitors and CAR T cell therapies.

Chronic exercise is linked to better physical fitness and a healthier immune profile, including reduced dysfunctional T cells, suggesting that incorporating exercise into cancer treatment plans could lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and the immune system: taking steps to improve responses to cancer immunotherapy. Gustafson, MP., Wheatley-Guy, CM., Rosenthal, AC., et al.[2023]

CAR-T cell therapy has shown remarkable efficacy in treating B cell malignancies, including leukemia, lymphoma, and multiple myeloma, with high response rates, but it comes with significant safety concerns.

The most serious side effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require supportive care and specific treatments like tocilizumab and steroids to manage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. Chohan, KL., Siegler, EL., Kenderian, SS.[2023]

Acute cycling exercise significantly increases the number of NKT-like cells in the blood, which show enhanced anti-tumor activity due to upregulated genes related to cytotoxicity and migration.

Despite the increase in NKT-like cells after exercise, this did not improve the ex vivo expansion of CIK cells, which remained equally effective at killing cancer cells regardless of whether they were expanded at rest or during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute exercise mobilizes NKT-like cells with a cytotoxic transcriptomic profile but does not augment the potency of cytokine-induced killer (CIK) cells. Zúñiga, TM., Baker, FL., Smith, KA., et al.[2022]

CAR T-cell therapy has shown durable remission in B-cell leukemia and lymphoma, highlighting its potential effectiveness for treating other types of cancers.

Recent advancements in CAR design and clinical application strategies aim to enhance T-cell proliferation and efficacy while minimizing toxicity, making this therapy more accessible to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cells: New Approaches to Improve Their Efficacy and Reduce Toxicity. Maus, MV., Powell, DJ.[2018]

The study shows that using a Clec9A-targeting nanoemulsion (Clec9A-TNE) vaccine can enhance the effectiveness of CAR T-cell therapy against solid tumors by improving T-cell activation and proliferation in mouse models.

Combining Clec9A-TNE with CAR T cells led to durable tumor responses and even tumor rejections, indicating a promising strategy to overcome challenges in treating solid tumors with CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing chimeric antigen receptor T-cell immunotherapy against cancer using a nanoemulsion-based vaccine targeting cross-presenting dendritic cells. Chan, JD., von Scheidt, B., Zeng, B., et al.[2022]

Exercise mobilizes specific types of immune cells, particularly NK-cells and effector-memory CD8+ T-cells, which have enhanced anti-tumor properties, as shown by single-cell RNA sequencing analysis.

In a study involving xenogeneic mice with human leukemia, mice receiving exercise-mobilized lymphocytes showed significantly lower tumor burden and improved survival rates compared to those receiving resting lymphocytes, without increasing the risk of graft-versus-host disease (GvHD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human lymphocytes mobilized with exercise have an anti-tumor transcriptomic profile and exert enhanced graft-versus-leukemia effects in xenogeneic mice. Batatinha, H., Diak, DM., Niemiro, GM., et al.[2023]

CAR-T cell therapy has shown remarkable success in treating B-cell malignancies, but researchers are focused on improving its safety and effectiveness due to risks like cytokine release syndrome and off-target effects.

Innovative safety strategies, such as ON- and OFF-switch CARs and multi-antigen-targeting CAR-T cells, are being developed to enhance the persistence and reduce adverse events associated with CAR-T therapy, paving the way for a new generation of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. Andrea, AE., Chiron, A., Bessoles, S., et al.[2023]

Exercise training (ExTr) significantly delays tumor growth in breast cancer models by normalizing tumor vasculature and enhancing CD8+ T-cell infiltration, which is crucial for its antitumor effects.

The study found that ExTr not only improves the immune tumor microenvironment but also enhances the effectiveness of immune checkpoint blockade therapies, suggesting a potential strategy to boost immunotherapy responses in breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Training Improves Tumor Control by Increasing CD8+ T-cell Infiltration via CXCR3 Signaling and Sensitizes Breast Cancer to Immune Checkpoint Blockade. Gomes-Santos, IL., Amoozgar, Z., Kumar, AS., et al.[2022]

CAR T-cell therapy is an effective treatment for acute lymphocytic leukemia and B-cell lymphoma, but it requires at least 7 days of hospitalization to monitor for serious side effects like cytokine release syndrome and neurotoxicity.

Early identification and treatment of these toxicities by nursing staff can reverse potentially life-threatening complications, highlighting the importance of objective assessment and consensus grading in managing CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Emergencies: Inpatient Administration, Assessment, and Management. Jackson, S., Wheatley, T.[2021]

A review of 152 pre-clinical studies on CAR T-cell therapy revealed that only 7.9% were specifically designed to assess or improve safety, indicating a significant gap in safety evaluation prior to clinical use.

Key safety parameters, such as the use of immunocompetent animal models and comprehensive monitoring of physiological responses, were inadequately reported, suggesting that current pre-clinical data may not reliably predict the safety of CAR T-cell therapies in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality Assessment of Pre-Clinical Studies of Chimeric Antigen Receptor T-Cell Therapy Products: A Point of Focus on Safety. Maharshi, V., Diksha, D., Gupta, P.[2022]

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