Mobilising Tumour and Immune Cells Via Exercise in Chronic Lymphocytic Leukaemia
Chronic Lymphocytic Leukemia, Minimal Residual Disease
About this trial
This is an interventional basic science trial for Chronic Lymphocytic Leukemia focused on measuring Exercise, Immunotherapy, Lymphocytes, ADCC
Eligibility Criteria
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.
Sites / Locations
- Royal United Hospital Bath NHS Foundation Trust
- University of Bath
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Cohort 1: Pre-treatment CLL
Cohort 2: During treatment CLL
Cohort 3: Post-treatment CLL
This group comprises patients who are diagnosed with CLL, but are asymptomatic and not receiving anti-CLL treatments (e.g. watch-and-wait disease).
This group comprises patients who are diagnosed with CLL, have symptomatic disease, and are undergoing anti-CLL treatments (e.g. chemo-immunotherapy).
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.