Mobilising Tumour and Immune Cells Via Exercise in Chronic Lymphocytic Leukaemia

Cohort 1 (Pre Treatment)

Inclusion criteria:

* 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)

Inclusion criteria:

* 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).
    * Fevers of 38.0°C or higher for 2 or more weeks without evidence of infection.
    * Night sweats for at least 1 month without evidence of infection.
* Recently initiated first-line treatment on one of the following regimes:

  * Fludarabine, cyclophosphamide and rituximab (FCR)
  * Ibrutinib monotherapy (I)
  * Ibrutinib + venetoclax (I+V)
  * Obinutuzumab + chlorambucil (O+C)
  * Bendamustine + rituximab (B+R)
  * Chlorambucil + ofatumumab (C+O)
  * Idelalisib + rituximab (I+R)
  * Venetoclax + rituximab (V+R)
  * Obinutuzumab monotherapy
  * Rituximab monotherapy
  * Ofatumumab monotherapy
  * Rituximab and chlorambucil
  * Chlorambucil monotherapy
* Ibrutinib or venetoclax maintenance treatment despite achieving complete remission (CR), complete remission with incomplete marrow recovery (CRi) or partial remission (PR).

Cohort 3 (Post treatment)

Inclusion criteria:

* 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.
* 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.

Exclusion criteria:

* 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.