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

NCT05178342 | Terminated Phase 2

• 1 other identifier: LUCAS
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 15

Brief Summary

Anemia in LR-MDS patients

Conditions

Myelodysplastic Syndromes; Anemia

Keywords

MDS; Anemia; Myelodysplastic Syndrome; IRAK4

Outcome Measures

Primary Outcomes (1)

• Erythroid response (HI-E)

  To evaluate the proportion of patients who have an erythroid response (HI-E) according to the modified IWG 2018 criteria separately for both independent substudies.

  At the end of cycle 4 (each cycle is 28 days).

Secondary Outcomes (9)

• HI-E response (erythroid response) duration

  From the date of treatment start until date of documented loss of response, assessed up to 30 months.

• Time to HI-E (erythroid response)

  From the date of treatment start until first day of response, assessed up to end of cycle 4 (each cycle is 28 days).

• Red blood cell (RBC) transfusions

  From the date of treatment start until the date of end of treatment, assessed up to 30 months.

• Neutrophil (HI-N) responses

  At the end of cycle 4 (each cycle is 28 days).

• Platelet (HI-P) responses

  At the end of cycle 4 (each cycle is 28 days).

Study Arms (1)

CA-4948 treatment

OTHER

Single-arm design. all patients are treated with IMP

Drug: CA-4948

Interventions

CA-4948 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.

Also known as: Emavusertib

CA-4948 treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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
• Defined transfusion strategy
• 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

You may not qualify if:

• 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
• Serum creatinine \> 2 × ULN or calculated creatinine clearance \< 30 ml/min
• AST \> 2 × ULN or ALT \> 2 × ULN
• 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
• Major surgery within 28 days prior to registration
• Concomitant diseases

Sponsors & Collaborators

• University of Leipzig: lead
• Curis, Inc.: collaborator

Study Sites (15)

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

Berlin, 12200, Germany

Location

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

Cottbus, 03048, Germany

Location

Gemeinschaftspraxis Dr. Jacobasch Dresden, Hämatologie Onkologie

Dresden, 01307, Germany

Location

Marienhospital Düsseldorf, Klinik für Onkologie und Hämatologie, Palliativmedizin

Düsseldorf, 40479, Germany

Location

ONCOSEARCH, Institut für Klinische Studien GbR

Erlangen, 91052, Germany

Location

InVO-Institut für Versorgungsforschung in der Onkologie

Koblenz, 56068, Germany

Location

VK & K Studien GbR, Studienzentrum

Landshut, 84036, Germany

Location

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

Leipzig, 04103, Germany

Location

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

Lübeck, 23538, Germany

Location

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

Mainz, 55131, Germany

Location

Universitätsklinikum Mannheim, III. Medizinische Klinik - Hämatologie und Onkologie

Mannheim, 68167, Germany

Location

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

Meschede, 59872, Germany

Location

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

München, 81675, Germany

Location

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

Neumünster, 24534, Germany

Location

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

Winnenden, 71364, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia

Interventions

CA-4948

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Uwe Platzbecker, Prof. Dr.

  University Leipzig

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: January 5, 2022
• Study Start: January 1, 2022
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (15)