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

Overview

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.

Interventions

• Other Exercise
  Weekly supervised exercise for 12 weeks followed by 12 weeks of non-supervised exercise
• Other Control
  Remain usual activity level

Primary outcome measures

• Exercise feasibility: Exercise sessions attendance [Time frame: From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Exercise feasibility: Recruitment, refusal, and retention rates [Time frame: From baseline until end of intervention (24 weeks)]
• Incidence of Adverse Events (AEs) [Time frame: From baseline until the end of intervention (24 weeks)]
• Incidence of Serious Adverse Events (SAEs) [Time frame: From baseline until the end of intervention (24 weeks)]

Secondary outcome measures (12)

• Changes in peak oxygen consumption (VO2 peak) [Time frame: From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Aerobic Capacity: Peak power output [Time frame: From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Muscle strength: Hand grip strength [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Functional performance: Habitual gait speed [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Functional performance: 30 seconds Sit-to-stand [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Body composition and anthropometrics: Body mass [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Body composition and anthropometrics: Total lean mass [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Body composition and anthropometrics: Total fat mass [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Body composition and anthropometrics: Bone mineral density [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Blood biochemistry: C-reactive protein [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Blood biochemistry: Insulin [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]
• Changes in Blood biochemistry: Glucose [Time frame: From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

Denmark · 2 centers

• Rigshospitalet — Copenhagen
• Rigshospitalet — Copenhagen

Identifiers

NCT: NCT06773871 · H-23022425

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗