We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    LUCAS | MDS | Leipzig, Germany
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05178342
Recruitment Status : Recruiting
First Posted : January 5, 2022
Last Update Posted : November 9, 2022
Sponsor:
Collaborator:
Curis, Inc.
Information provided by (Responsible Party):
Uwe Platzbecker, University of Leipzig

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Anemia in LR-MDS patients

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Anemia Drug: CA-4948 Phase 2

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
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label, Multicenter Study of Orally Administered CA-4948 for the Treatment of Anemia in Patients With Very Low, Low or Intermediate Risk Myelodysplastic Syndromes (MDS)
Actual Study Start Date : January 1, 2022
Estimated Primary Completion Date : April 2024
Estimated Study Completion Date : April 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
CA-4948 treatment
Single-arm design. all patients are treated with IMP
 Drug: 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.

Other Name: Emavusertib


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Erythroid response (HI-E) [ Time Frame: At the end of cycle 4 (each cycle is 28 days). ]
    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.


Secondary Outcome Measures :
  1. HI-E response (erythroid response) duration [ Time Frame: From the date of treatment start until date of documented loss of response, assessed up to 30 months. ]
    To evaluate HI-E response from the first day of response until loss of response.

  2. Time to HI-E (erythroid response) [ Time Frame: From the date of treatment start until first day of response, assessed up to end of cycle 4 (each cycle is 28 days). ]
    To evaluate the time between start of treatment and first day of response.

  3. Red blood cell (RBC) transfusions [ Time Frame: From the date of treatment start until the date of end of treatment, assessed up to 30 months. ]
    To evaluate frequency of red blood cell transfusions in transfusion dependent patients

  4. Neutrophil (HI-N) responses [ Time Frame: At the end of cycle 4 (each cycle is 28 days). ]
    Neutrophil (HI-N) responses according to IWG 2018 criteria

  5. Platelet (HI-P) responses [ Time Frame: At the end of cycle 4 (each cycle is 28 days). ]
    Platelet (HI-P) responses according to IWG 2018 criteria

  6. Safety of CA-4948 (toxicities and adverse events) [ Time Frame: From the date of treatment start until the end of study, assessed up to 30 months. ]
    Assessments will include characterization of toxicities; characterization of AEs including type, incidence, severity, seriousness, and relationship to treatment

  7. Number of participants with clinically significant changes of selected laborotory parameters (parameters listed in detailed description) [ Time Frame: From the date of treatment start until the end of study, assessed up to 30 months. ]
    To ensure patient safety, close monitoring is carried and includes the analysis of: transaminases, bilirubin, amylase, lipase, troponin, lactate dehydrogenase, creatine kinase, uric acid, TSH, FT4, urine analysis.

  8. Impact of treatment assessed by using the validated European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) [ Time Frame: From the date of treatment start until the end of study, assessed up to 30 months. ]

    To assess patient-reported quality of life during CA-4948 treatment: 30 questions assessing the quality of life of oncology patients across 10 subscales will be analyzed. All subscales have a score range from 0 to 100 points.

    Function subscales: a higher score represents a higher quality of life. Symptoms subscales: higher score represents higher level of symptoms/problems, i.e., represents lower quality of life.


  9. Impact of treatment assessed by using the validated European Organisation for Research and Treatment of Cancer cancer related fatigue questionnaire (EORTC QLQ- FA12) [ Time Frame: From the date of treatment start until the end of study, assessed up to 30 months. ]
    To assess patient-reported quality of life during CA-4948 treatment: 12 items, with four response categories for each item (coded with values from 1 to 4) will be analyzed. FA12 scores are transformed to the range 0-100: Higher levels indicate greater degrees of fatigue.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05178342


Contacts
Layout table for location contacts
Contact: Uwe Platzbecker, Prof. Dr. +49 341 97 13050 uwe.platzbecker@medizin.uni-leipzig.de
Contact: Anne Sophie Kubasch, Dr. annesophie.kubasch@medizin.uni-leipzig.de

Locations
Layout table for location information
Germany
Charité Berlin - Campus Benjamin Franklin, Med. Klinik m. S. Hämatologie, Onkologie, Tumorimmunologie Recruiting
Berlin, Germany, 12200
Contact: Kathrin Rieger, Dr.         
Carl-Thiem-Klinikum Cottbus gGmbH, 2. Med. Klinik Recruiting
Cottbus, Germany, 03048
Contact: Martin Schmidt-Hieber, PD Dr.         
Gemeinschaftspraxis Dr. Jacobasch Dresden, Hämatologie Onkologie Recruiting
Dresden, Germany, 01307
Contact: Thomas Illmer, PD Dr.         
Marienhospital Düsseldorf, Klinik für Onkologie und Hämatologie, Palliativmedizin Recruiting
Düsseldorf, Germany, 40479
Contact: Aristoteles Giagounidis, Prof. Dr.         
ONCOSEARCH, Institut für Klinische Studien GbR Recruiting
Erlangen, Germany, 91052
Contact: Martina Haibach, Dr.         
InVO-Institut für Versorgungsforschung in der Onkologie Recruiting
Koblenz, Germany, 56068
Contact: Rudolf Weide, Prof. Dr.         
VK & K Studien GbR, Studienzentrum Recruiting
Landshut, Germany, 84036
Contact: Ursula Vehling-Kaiser, Dr.         
University Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie Recruiting
Leipzig, Germany, 04103
Contact: Uwe Platzbecker, Prof. Dr.         
Universitätsklinikum Schleswig-Holstein, Klinik für Hämatologie und Onkologie Campus Lübeck Not yet recruiting
Lübeck, Germany, 23538
Contact: Friederike Wortmann, Dr.         
Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik - Hämatologie, Internistische Onkologie und Pneumologie Recruiting
Mainz, Germany, 55131
Contact: Markus Radsak, Prof. Dr.         
Universitätsklinikum Mannheim, III. Medizinische Klinik - Hämatologie und Onkologie Recruiting
Mannheim, Germany, 68167
Contact: Mohamad Jawhar, PD Dr.         
Klinikum Hochsauerland GmbH, Klinik f. Hämatologie, Onkologie, Palliativmedizin, Stammzelltransplantation Recruiting
Meschede, Germany, 59872
Contact: Mohammad Amen Wattad, Dr.         
Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie Not yet recruiting
München, Germany, 81675
Contact: Katharina Götze, Prof. Dr.         
Friedrich-Ebert-Krankenhaus GmbH, Klinik für Hämatologie, Onkologie und Nephrologie Recruiting
Neumünster, Germany, 24534
Contact: Stefan Mahlmann, Dr.         
Rems-Murr-Kliniken gGmbH, Hämatologie, Onkologie und Palliativmedizin Recruiting
Winnenden, Germany, 71364
Contact: Alexander Reichart, Prof. Dr.         
Sponsors and Collaborators
University of Leipzig
Curis, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Uwe Platzbecker, Prof. Dr. University Leipzig
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Uwe Platzbecker, Prof. Dr., University of Leipzig
ClinicalTrials.gov Identifier: NCT05178342    
Other Study ID Numbers: LUCAS
First Posted: January 5, 2022    Key Record Dates
Last Update Posted: November 9, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Uwe Platzbecker, University of Leipzig:
MDS
Anemia
Myelodysplastic Syndrome
IRAK4
Additional relevant MeSH terms:
Layout table for MeSH terms
Preleukemia
Anemia
Myelodysplastic Syndromes
Syndrome
Disease
 Pathologic Processes
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms