Clinical trial NCT06773871: Feasibility and Safety of Exercise in Patients with Low-risk Myeloid Cancers and Precursor Conditions
Official title: Feasibility and Safety of Exercise in Patients with Low-risk (or Early-stage) Myeloid Cancers and Precursor Conditions (HemEx): a Randomized Controlled Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Myelodysplastic Syndrome
Cytopenia
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2025-01-14
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Treatment with chemotherapy, therapeutic radiation, or immunosuppressive therapy within the last year
* Treatment with hypomethylating agents
* Any absolute contraindication to undergo cardiopulmonary exercise testing according to working papers from American Heart Association and Danish Society of Cardiology
* Hemoglobin levels \< 5.5 mmol OR \<6.5 mmol and simultaneous cardiac insufficiency OR pacemaker.
* Blood transfusion-dependent ≥ 8 units of red blood cell transfusion in 16 weeks (IWG 2018-criteria)
* Uncontrolled co-morbidity

Primary outcomes:
measure: Exercise feasibility: Exercise sessions attendance
timeFrame: From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Exercise feasibility: Recruitment, refusal, and retention rates
timeFrame: From baseline until end of intervention (24 weeks)
measure: Incidence of Adverse Events (AEs)
timeFrame: From baseline until the end of intervention (24 weeks)
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: From baseline until the end of intervention (24 weeks)
Secondary outcomes:
measure: Changes in peak oxygen consumption (VO2 peak)
timeFrame: From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Aerobic Capacity: Peak power output
timeFrame: From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Muscle strength: Hand grip strength
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Functional performance: Habitual gait speed
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Functional performance: 30 seconds Sit-to-stand
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Body composition and anthropometrics: Body mass
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Body composition and anthropometrics: Total lean mass
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Body composition and anthropometrics: Total fat mass
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Body composition and anthropometrics: Bone mineral density
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: C-reactive protein
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: Insulin
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: Glucose
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: Triglycerides
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: LDL-Cholesterol
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: HDL-Cholesterol
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: Total Cholesterol
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: HbA1c
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: total bilirubin
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: Vitamin D (25-Hydroxy-Vitamin D(D3+D2))
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: insulin growth factor 1 (IGF-1)
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: human growth hormone (HGH)
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: sex hormones (estrogen, progesterone and testosterone)
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Cytokine levels in blood: Interleukin-6
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Cytokine levels in blood: Tumor-necrosis-factor alpha (TNFalpha)
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Patient-reported symptomatic adverse events
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Inflammatory markers in Bone marrow (BM) and peripheral blood
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Regulate the immune cell composition in the BM
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Change the variant allele frequency (VAF)
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Alter the composition of BMAT
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Ifluence on the cytopenia(s)
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
measure: Changes in Blood biochemistry: Lactate dehydrogenase (LDH)
timeFrame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
References: