Treatment of Anemia in Patients With Very Low, Low or Intermediate Risk Myelodysplastic Syndromes With CA-4948

Inclusion Criteria: 1. Diagnosis of de novo myelodysplastic syndrome (MDS) OR de novo myelodysplastic/myeloproliferative neoplasias (MDS/MPN) including MDS/MPN-RS-T, MDS/MPNu, aCML or CMML 2. Very low/low/intermediate risk disease: IPSS-R up to 3.5 for MDS; MDS/MPN \< 10% bone marrow blasts; for CMML low or intermediate risk according to CPSS-Score 3. Symptomatic anemia (based on valid and complete hemoglobin and transfusion history): * NTD (non transfusion dependent): \< 3 RBC transfusions and mean hemoglobin level \<10 g/dl within the last 16 weeks * LTB (low transfusion burden): 3-7 RBC transfusions within the last 16 weeks in at least two transfusion episodes, maximum 3 in 8 weeks * HTB (high transfusion burden): ≥ 8 RBC transfusions within the last 16 weeks, ≥ 4 in 8 weeks 4. Defined transfusion strategy 5. No available option of an approved MDS therapy and classification of prior erythropoiesis-stimulating agent (ESA) treatment as follows: * Cohort A: ESA exposed (and refractory or intolerant) * Cohort B: ESA naive AND serum erythropoietin level \>200 U/L Exclusion Criteria: Compliance with major study procedures * Inability to swallow and retain oral medications (\> 10 pills) * Patient does not accept bone marrow sampling during screening and after the treatment * Patient does not accept up to weekly peripheral blood sampling during screening and treatment Safety * ECOG performance status ≥ 3 * Inacceptable organ function 1. Serum creatinine \> 2 × ULN or calculated creatinine clearance \< 30 ml/min 2. AST \> 2 × ULN or ALT \> 2 × ULN 3. total bilirubin \> 2 × ULN (exception \>3 × ULN in patients with documented Gilbert's syndrome) Interfering treatments * Prior treatment with azacitidine or decitabine * Treatment with erythropoiesis stimulating agent (ESA), G-CSF, GM-CSF, lenalidomide, luspatercept and/or another investigational drug or device up to 14 days before registration * Treatment with iron chelation therapy 56 days before registration, except for subjects on a stable or decreasing dose for at least eight weeks prior to inclusion and during study treatment * Major surgery within 28 days prior to registration Concomitant diseases * Known human immunodeficiency virus infection (HIV) * Active infectious hepatitis (HBV or HCV) * Hepatitis virus detectable within 6 months before registration in patients with a history of hepatitis * History of other invasive malignancy, unless definitively treated with curative intent, provided it is deemed to be at low risk for recurrence by the treating physician * Presence of an acute or chronic toxicity resulting from prior anti-cancer therapy that has not resolved to Grade ≤ 1 (except anemia and alopecia) * Known allergy or hypersensitivity to any component of the formulation of CA-494824 * Severe cardiovascular disease (e.g. myocardial infarction within 6 months registration, unstable angina within 6 months registration, NYHA Class III or greater congestive heart failure, serious arrhythmias uncontrolled on treatment, clinically significant pericardial disease, known QTc abnormality \> 450 msec on ECG Formal requirements * Positive serum pregnancy test in women of childbearing potential * Women of childbearing potential and men who partner with a woman of childbearing potential unwilling to use highly effective contraceptive methods for the duration of the study and for 90 days after the last dose of CA-4948 * Age under 18 years at registration * Inability to provide written informed consent * Simultaneous participation in another interventional clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 28 days prior registration