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

August 12, 2024 updated by: Uwe Platzbecker, University of Leipzig

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)

Anemia in LR-MDS patients

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
38

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
      • Berlin, Germany, 12200
        • Charité Berlin - Campus Benjamin Franklin, Med. Klinik m. S. Hämatologie, Onkologie, Tumorimmunologie
      • Cottbus, Germany, 03048
        • Carl-Thiem-Klinikum Cottbus gGmbH, 2. Med. Klinik
      • Dresden, Germany, 01307
        • Gemeinschaftspraxis Dr. Jacobasch Dresden, Hämatologie Onkologie
      • Düsseldorf, Germany, 40479
        • Marienhospital Düsseldorf, Klinik für Onkologie und Hämatologie, Palliativmedizin
      • Erlangen, Germany, 91052
        • ONCOSEARCH, Institut für Klinische Studien GbR
      • Koblenz, Germany, 56068
        • InVO-Institut für Versorgungsforschung in der Onkologie
      • Landshut, Germany, 84036
        • VK & K Studien GbR, Studienzentrum
      • Leipzig, Germany, 04103
        • University Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie
      • Lübeck, Germany, 23538
        • Universitätsklinikum Schleswig-Holstein, Klinik für Hämatologie und Onkologie Campus Lübeck
      • Mainz, Germany, 55131
        • Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik - Hämatologie, Internistische Onkologie und Pneumologie
      • Mannheim, Germany, 68167
        • Universitätsklinikum Mannheim, III. Medizinische Klinik - Hämatologie und Onkologie
      • Meschede, Germany, 59872
        • Klinikum Hochsauerland GmbH, Klinik f. Hämatologie, Onkologie, Palliativmedizin, Stammzelltransplantation
      • München, Germany, 81675
        • Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie
      • Neumünster, Germany, 24534
        • Friedrich-Ebert-Krankenhaus GmbH, Klinik für Hämatologie, Onkologie und Nephrologie
      • Winnenden, Germany, 71364
        • Rems-Murr-Kliniken gGmbH, Hämatologie, Onkologie und Palliativmedizin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 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 Names:
  • Emavusertib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
At the end of cycle 4 (each cycle is 28 days).

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
From the date of treatment start until date of documented loss of response, assessed up to 30 months.
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.
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
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
From the date of treatment start until the date of end of treatment, assessed up to 30 months.
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
At the end of cycle 4 (each cycle is 28 days).
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
At the end of cycle 4 (each cycle is 28 days).
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
From the date of treatment start until the end of study, assessed up to 30 months.
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.
From the date of treatment start until the end of study, assessed up to 30 months.
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.
From the date of treatment start until the end of study, assessed up to 30 months.
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.
From the date of treatment start until the end of study, assessed up to 30 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Leipzig

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Curis, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Uwe Platzbecker, Prof. Dr., University Leipzig

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 2, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 5, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 13, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 12, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LUCAS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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