Feasibility and Safety of Exercise in Patients With Low-risk (or Early-stage) Myeloid Cancers and Precursor Conditions (HemEx): a Randomized Controlled Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
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:
- whether an exercise intervention and the trial set-up, are feasible and safe in this cohort,
- potential mechanisms in leukemogenesis affected by exercise in controlling dis-ease progression,
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: From baseline until the end of intervention (24 weeks)
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.
Exercise feasibility: Exercise sessions attendance
时间窗: From baseline until the end of12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.
The number of attended exercise training sessions relative to the number of planned exercise sessions
Exercise feasibility: Recruitment, refusal, and retention rates
时间窗: From baseline until end of intervention (24 weeks)
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
Incidence of Serious Adverse Events (SAEs)
时间窗: From baseline until the end of intervention (24 weeks)
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.
次要结局
- Changes in peak oxygen consumption (VO2 peak)(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(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(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(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(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(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(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(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(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(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: Insulin(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: Glucose(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: Triglycerides(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: LDL-Cholesterol(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: HDL-Cholesterol(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: Total Cholesterol(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: HbA1c(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: human growth hormone (HGH)(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: sex hormones (estrogen, progesterone and testosterone)(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Cytokine levels in blood: Tumor-necrosis-factor alpha (TNFalpha)(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Inflammatory markers in Bone marrow (BM) and peripheral blood(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Regulate the immune cell composition in the BM(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Alter the composition of BMAT(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: total bilirubin(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: Vitamin D (25-Hydroxy-Vitamin D(D3+D2))(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: insulin growth factor 1 (IGF-1)(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Cytokine levels in blood: Interleukin-6(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Patient-reported symptomatic adverse events(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Change the variant allele frequency (VAF)(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Ifluence on the cytopenia(s)(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
- Changes in Blood biochemistry: Lactate dehydrogenase (LDH)(From baseline until the end of 12 weeks of supervised exercise. And after 12 weeks of no supervised exercise.)
研究者
Kirsten Grønbæk
Professor, MD
Rigshospitalet, Denmark