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

• Status: Not yet recruiting
• Trial end date: 2025-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Anemia in patients with very low, low or intermediate risk myelodysplastic syndromes (MDS)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Leipzig
• Collaborator: Curis, Inc.

Criteria

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