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

NCT ID: NCT05178342

Last Updated: 2024-08-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2024-07-31

Brief Summary

Anemia in LR-MDS patients

Detailed Description

Anemia in non-transfusion dependent (NTD) or transfusion dependent (low or high transfusion burden, LTB/HTB) patients with very low, low or intermediate risk myelodysplastic syndromes

Conditions

Myelodysplastic Syndromes; Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CA-4948 treatment

Single-arm design. all patients are treated with IMP

Group Type: OTHER

CA-4948

Intervention Type: DRUG

Patients will be treated orally with CA-4948 at 300 mg BID (2x200mg) over 4 cycles. One cycle consists of 28 days, 21 of which are treatment days, followed by 7 days off.

Patients with erythroid response (HI-E) after 4 cycles who tolerate CA-4948 may continue to receive CA-4948 until loss of HI-E response.

Interventions

CA-4948

Patients will be treated orally with CA-4948 at 300 mg BID (2x200mg) over 4 cycles. One cycle consists of 28 days, 21 of which are treatment days, followed by 7 days off.

Patients with erythroid response (HI-E) after 4 cycles who tolerate CA-4948 may continue to receive CA-4948 until loss of HI-E response.

Intervention Type: DRUG

Other Intervention Names

Emavusertib

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Curis, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Leipzig

OTHER

Sponsor Role: lead

Responsible Party

Uwe Platzbecker

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Uwe Platzbecker, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Leipzig

Locations

Charité Berlin - Campus Benjamin Franklin, Med. Klinik m. S. Hämatologie, Onkologie, Tumorimmunologie

Berlin, , Germany

Carl-Thiem-Klinikum Cottbus gGmbH, 2. Med. Klinik

Cottbus, , Germany

Gemeinschaftspraxis Dr. Jacobasch Dresden, Hämatologie Onkologie

Dresden, , Germany

Marienhospital Düsseldorf, Klinik für Onkologie und Hämatologie, Palliativmedizin

Düsseldorf, , Germany

ONCOSEARCH, Institut für Klinische Studien GbR

Erlangen, , Germany

InVO-Institut für Versorgungsforschung in der Onkologie

Koblenz, , Germany

VK & K Studien GbR, Studienzentrum

Landshut, , Germany

University Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie

Leipzig, , Germany

Universitätsklinikum Schleswig-Holstein, Klinik für Hämatologie und Onkologie Campus Lübeck

Lübeck, , Germany

Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik - Hämatologie, Internistische Onkologie und Pneumologie

Mainz, , Germany

Universitätsklinikum Mannheim, III. Medizinische Klinik - Hämatologie und Onkologie

Mannheim, , Germany

Klinikum Hochsauerland GmbH, Klinik f. Hämatologie, Onkologie, Palliativmedizin, Stammzelltransplantation

Meschede, , Germany

Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie

München, , Germany

Friedrich-Ebert-Krankenhaus GmbH, Klinik für Hämatologie, Onkologie und Nephrologie

Neumünster, , Germany

Rems-Murr-Kliniken gGmbH, Hämatologie, Onkologie und Palliativmedizin

Winnenden, , Germany

Countries

Germany

Other Identifiers

LUCAS

Identifier Type: -

Identifier Source: org_study_id