CCUS Clonal Cytopenia of Undetermined Significance

To learn if olutasidenib can help to control CCUS, MDS, and/or CMML. The safety of the drug will also be studied.

Somatic mutations as seen in myeloid malignancies can also be detected in healthy, elderly individuals (clonal hematopoiesis of indeterminate potential, CHIP), in patients with unexplained cytopenia, that do not fulfill the criteria for myeloid malignancy (clonal cytopenia of undetermined significance, CCUS) It has been shown that these conditions predispose to hematological cancer and 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 leukemia (AML), both devastating diseases with poor outcomes, especially for the elderly population. 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 a potential for early intervention.
Overweight and physical inactivity are 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 inflammation 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 microenvironment play a crucial role; factors that exercise may modulate. In addition, recent studies have shown that increased bone marrow adipose tissue (BMAT) may create a microenvironment that supports the expansion of leukemic cells and thus may facilitate disease progression, and earlier studies among healthy, younger individuals have shown that exercise can reduce the amount of BMAT significantly.
We therefore hypothesize, that exercise may prevent or delay the progression from pre-leukemia to leukemia by altering the microenvironment in the bone marrow.
Our 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 intervention is to investigate:
1. whether an exercise intervention, and the trial set-up, is feasible and safe in this cohort,
2. potential mechanisms in leukemogenesis affected by exercise in controlling disease 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.

Study researchers think that a drug called enasidenib may help people with clonal cytopenia of undetermined significance (CCUS) because the drug blocks the mutated IDH2 protein, which may improve blood cell counts. The purpose of this study is to find out whether enasidenib is a safe and effective treatment for CCUS.