Feasibility and Safety of Exercise in Patients With Low-risk Myeloid Cancers and Precursor Conditions
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorRigshospitalet, Denmark
About this trial
Somatic mutations as seen in myeloid malignancies can also be detected in healthy, elderly individuals (clonal hematopoiesis of indeterminate potential, CHIP), in patients with unex-plained cytopenia, that do not fulfill the criteria for myeloid malignancy (clonal cytopenia of un-determined significance, CCUS) It has been shown that these conditions predispose to hema-tological cancer. For patients with CCUS, it has been reported that in a 5-year period up to 50-90 % of the patients will progress to myelodysplastic syndrome (MDS) or acute myeloid leu-kemia (AML), both devastating diseases with poor outcomes, especially for the elderly popula-tion. There is currently no treatment available for patients with CCUS besides supporting agents. Since the somatic mutations can be detected up to 10 years before a diagnosis of MDS, it opens the potential for early intervention.
Physical inactivity is associated with multiple solid cancers, and it has been suggested that exercise can prevent for example certain colon- or breast cancers. Studies in mice have shown that exercise can reduce tumor size and incidence of solid cancers, and different mechanisms have been suggested including increased immune cell infiltration, reduced systemic inflamma-tion, and metabolic changes. The mechanisms of disease progression of pre-leukemia and MDS are complex and probably multifactorial, but recent studies suggest that components such as natural killer cells, adipocytes, and inflammatory substances in the bone marrow mi-croenvironment play a crucial role; factors that exercise may modulate. In addition, recent stud-ies have shown that increased bone marrow adipose tissue (BMAT) may create a microenvi-ronment that supports the expansion of leukemic cells and thus may facilitate disease progres-sion, and earlier studies among healthy, younger individuals have shown that exercise can reduce the amount of BMAT significantly.
Therefore, the investigators hypothesize that exercise may prevent or delay the progression from pre-leukemia to leukemia by altering the microenvironment in the bone marrow.
The purpose with this clinical, pilot trial where patients with the preleukemic condition CCUS or early stage of leukemia (i.e., lower-risk MDS) will undergo an individualized exercise interven-tion, is to investigate:
1. whether an exercise intervention and the trial set-up, are feasible and safe in this cohort, 2. potential mechanisms in leukemogenesis affected by exercise in controlling dis-ease progression, 3. and the effect hereof on quality of life and activities of daily living. The above will inform the decision-making on designing a larger randomized, controlled trial.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
A diagnosis of either Lower-risk of Myelodysplastic Syndrome or Clonal Cytopenia of undetermined significance(WHO 2022 Classification)
Written informed consent prior to study procedures
Performance status ≤ 2
Age > 18 years old
Disqualifiers
Physically not able to undergo exercise intervention (e.g., arthrosis, physical disabilities)
Exercising on a regular basis (i.e., participants must score in the category "low" when screening with International Physical Activity Questionnaire-Short Form; IPAQ-SF27)
Unwillingness to undergo exercise intervention
Use of metformin
Trial design
Design model
Parallel
Treatments tested in this trial
Exercise
Other interventionWeekly supervised exercise for 12 weeks followed by 12 weeks of non-supervised exercise
Control
Other interventionRemain usual activity level
Treatment groups
36 Participants
are divided into 2 treatment groupsGroup A: ControlActive comparator 1 intervention
Group B: Exercise interventionExperimental treatment 0 interventions
Trial outcomes
Primary outcomes
1
Exercise feasibility: Exercise sessions attendance
The number of attended exercise training sessions relative to the number of planned exercise sessions
Time frame
From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.2
Exercise feasibility: Recruitment, refusal, and retention rates
The number of patients recruited to the study, the number of patients who refused to be enrolled in the study, the number of participants that completed the study
Time frame
From baseline until end of intervention (24 weeks)3
Incidence of Adverse Events (AEs)
AE will be recorded during trial assessment visits and through medical records. This procedure will concern any AE during the trial period. We will collect patients' self-report of AEs for each trial visit and telephone interview, which may have occurred since the last trial visit and telephone interview.
Time frame
From baseline until the end of intervention (24 weeks)4
Incidence of Serious Adverse Events (SAEs)
SAE will be recorded during trial assessment visits and through medical records. This procedure will concern any SAE during the trial period. We will collect patients' self-report of SAEs for each trial visit and telephone interview, which may have occurred since the last trial visit and telephone interview.
Time frame
From baseline until the end of intervention (24 weeks)Secondary outcomes
1
Changes in peak oxygen consumption (VO2 peak)
Changes in VO2peak assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer
Time frame
From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.2
Changes in Aerobic Capacity: Peak power output
Changes in peak power output assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer
Time frame
From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.3
Changes in Muscle strength: Hand grip strength
Changes in hand grip strength, assessed using a dynamometer
Time frame
From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.4
Changes in Functional performance: Habitual gait speed
Changes in habitual gait speed
Time frame
From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.Sponsors and contacts
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Source ClinicalTrials.gov