Mobilising Tumour and Immune Cells Via Exercise in Chronic Lymphocytic Leukaemia

NCT05093192 | Completed

• 1 other identifier: 272493
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

Chronic lymphocytic leukaemia (CLL) is the most common adult blood cancer in the United Kingdom. CLL means that many cancer cells appear in the blood, bone marrow and other tissues, for example, the spleen where some blood cells reside. Most patients with CLL have been diagnosed by chance, have no symptoms as a result of CLL, and do not need urgent treatment. However, when the cancer cells build up, people experience symptoms of CLL, and treatment is required. One of the current treatments for CLL is chemo-immunotherapy, that targets and kills cancer cells in the blood. However, this treatment does not kill all cancer cells. Some cancer cells survive by 'hiding' in the bone marrow and tissues, like the spleen, where the treatment cannot get to, this is called minimal residual disease (MRD). MRD eventually builds up and patients experience symptoms of CLL again. New approaches to detect and treat MRD are needed. Research has shown, that the number of blood cells, increases after exercise and that many of these blood cells come from the bone marrow and other tissues. This study will investigate if exercise can move CLL cancer cells that are 'hiding' in the bone marrow and other tissues into the blood, thus improving the detection of MRD. By moving cancer cells into blood, the investigators also think this will improve the way chemo-immunotherapy works. In this study, the investigators will investigate the number of cancer and natural killer (NK) cells in the blood after exercise, in three different groups of people with CLL: before treatment; during treatment; and after treatment has finished.

Conditions

Chronic Lymphocytic Leukemia; Minimal Residual Disease

Keywords

Exercise; Immunotherapy; Lymphocytes; ADCC

Outcome Measures

Primary Outcomes (1)

• Investigate whether an acute bout of exercise changes the frequency of CLL cells in peripheral blood.

  Number of CLL cells per microlitre will be measured by flow cytometry.

  Change from baseline CLL cell frequency to following 20-30 minutes of cycling.

Secondary Outcomes (9)

• Investigate whether an acute bout of exercise changes the frequency of immune cells (e.g., CD16+ NK cells), in peripheral blood.

  Change from baseline immune cell frequency to following 20-30 minutes of cycling.

• Investigate whether an acute bout of exercise changes the efficacy of anti-CD20 treatments against a CD20+ cell line or primary CLL cells.

  Change from baseline CD20+ cell lysis to following 20-30 minutes of cycling.

• Investigate whether an acute bout of exercise changes whole blood counts.

  Change from baseline whole blood counts to following 20-30 minutes of cycling.

• Investigate whether an acute bout of exercise changes immunoglobulins.

  Change from baseline immunoglobulins to following 20-30 minutes of cycling.

• Investigate whether an acute bout of exercise changes serum C1q.

  Change from baseline C1q to following 20-30 minutes of cycling.

Other Outcomes (18)

• Differences in physical fitness amongst groups along CLL survivorship spectrum.

  Baseline, pre-intervention.

• Differences in height amongst groups along CLL survivorship spectrum.

  Baseline, pre-intervention.

• Differences in weight amongst groups along CLL survivorship spectrum.

  Baseline, pre-intervention.

Study Arms (3)

Cohort 1: Pre-treatment CLL

EXPERIMENTAL

This group comprises patients who are diagnosed with CLL, but are asymptomatic and not receiving anti-CLL treatments (e.g. watch-and-wait disease).

Other: Exercise trial

Cohort 2: During treatment CLL

EXPERIMENTAL

This group comprises patients who are diagnosed with CLL, have symptomatic disease, and are undergoing anti-CLL treatments (e.g. chemo-immunotherapy).

Other: Exercise trial

Cohort 3: Post-treatment CLL

EXPERIMENTAL

This group comprises patients who were diagnosed with CLL, but are considered to be in either complete or partial remission following anti-CLL treatment for at least 6-months.

Other: Exercise trial

Interventions

Exercise trial OTHER

Participants will perform a supervised acute bout of aerobic exercise over 20-30 minutes, corresponding to a target power output at an intensity +10 to 15% above ventilatory threshold.

Cohort 1: Pre-treatment CLL; Cohort 2: During treatment CLL; Cohort 3: Post-treatment CLL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of: Chronic lymphocytic leukaemia. Defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines as the presence of 5000 B cells per µL of peripheral blood, sustained for at least 3 months and confirmed by the blood smear, immunophenotype and in some cases genetic features of lymphoid cells.
• Age \> 18 years old.
• Asymptomatic early-stage disease monitored without anti-CLL treatment.
• Cohort 2 (Treatment)
• A diagnosis of: Chronic lymphocytic leukaemia. Defined by iwCLL guidelines as the presence of 5000 B cells per µL of peripheral blood, sustained for at least 3 months and confirmed by the blood smear, immunophenotype and in some cases genetic features of lymphoid cells.
• Age \> 18 years old.
• Evidence of active disease defined as the following by the iwCLL guidelines:
• Evidence of progressive marrow failure-the development of, or worsening of, anaemia and/or thrombocytopenia (in some patients, platelet counts \<100 × 109/L may remain stable over a long period; this does not automatically require therapeutic intervention). Cut-off levels of haemoglobin less than 10 g/dL or platelet counts less than 100 × 109/L are generally regarded as an indication for treatment.
• Massive (i.e., ≥6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
• Massive nodes (i.e., ≥10 cm in longest diameter), progressive, or symptomatic lymphadenopathy.
• Progressive lymphocytosis with an increase of 50% or more over a 2-month period, or lymphocyte-doubling time (LDT) less than 6 months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; patients with initial blood lymphocyte counts less than 30 × 109/L may require a longer observation period to determine the LDT. Factors contributing to lymphocytosis other than CLL (e.g., infections or steroid administration) should be excluded.
• Autoimmune complications, including anaemia or thrombocytopenia that respond poorly to corticosteroids.
• Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung, or spine). Disease-related symptoms defined as any of the following:
• Unintentional weight loss of 10% or more within the previous 6 months.
• Significant fatigue (i.e., Eastern Cooperative Oncology Group performance scale 2 or worse, cannot work, or unable to perform usual activities).

You may not qualify if:

• World Health Organisation (WHO)/ Eastern Cooperative Oncology Group (ECOG) performance status \>1
• Pregnancy
• Deemed unsafe to exercise according to the Physical Activity Readiness Questionnaire (PARQ)
• Any comorbidity that is likely to progress or be exacerbated over the course of the trial period (e.g. history of syncopal events, significant cardiac or respiratory events)
• Cognitive impairment deemed a risk by the healthcare team for participation in the trial (e.g. diagnosis of neurodegenerative disease)
• Unable to understand explanations and/or provide informed consent
• Any condition and/or behaviour that would pose undue personal risk or introduce bias into the trial
• Following first-line treatment failure, patients with progressive disease or stable disease, as defined by iwCLL guidelines and described in Table 1 above.
• Recent b0lood counts at levels that are deemed to pose undue risk by the healthcare team.
• Any participant that has not received double coronavirus vaccinations, at least 14-days prior to the screening visit.

Sponsors & Collaborators

• University of Bath: lead
• Royal United Hospitals Bath NHS Foundation Trust: collaborator
• University of Southampton: collaborator
• Great Western Hospitals NHS Foundation Trust: collaborator

Study Sites (2)

Royal United Hospital Bath NHS Foundation Trust

Bath, Bath & Northeast Somerset, BA1 3NG, United Kingdom

Location

University of Bath

Bath, Bath & Northeast Somerset, BA2 7AY, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm, Residual; Motor Activity

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Behavior

Study Officials

• John P Campbell, PhD

  University of Bath

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A pilot, single-centre, Phase I trial containing 3 groups during different phases of CLL survivorship: * Cohort 1 (Pre treatment) CLL patients with asymptomatic early-stage disease monitored without anti-CLL treatment. * Cohort 2 (Treatment) Treatment eligible CLL patients receiving first-line anti-CLL treatment or patients receiving anti-CLL maintenance treatment. * Cohort 3 (Post treatment) CLL patients in complete remission (CR), complete remission with incomplete marrow recovery (CRi) or partial remission (PR) for at least 6 months following the completion of anti-CLL treatment. All participants will complete the study intervention.

Study Record Dates

• First Submitted: September 6, 2021
• First Posted: October 26, 2021
• Study Start: October 1, 2021
• Primary Completion: December 6, 2022
• Study Completion: December 6, 2022
• Last Updated: September 8, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)