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JOURNAL ONKOLOGIE – STUDIE
LUCAS

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

Rekrutierend

NCT-Nummer:
NCT05178342

Studienbeginn:
Januar 2022

Letztes Update:
21.08.2023

Wirkstoff:
CA-4948

Indikation (Clinical Trials):
Preleukemia, Anemia, Myelodysplastic Syndromes, Syndrome

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
University of Leipzig

Collaborator:
Curis, Inc.

Studienleiter

Uwe Platzbecker, Prof. Dr.
Principal Investigator
University Leipzig

Kontakt

Uwe Platzbecker, Prof. Dr.
Kontakt:
Phone: +49 341 97 13050
E-Mail: uwe.platzbecker@medizin.uni-leipzig.de» Kontaktdaten anzeigen

Studienlocations
(3 von 15)

Charité Berlin - Campus Benjamin Franklin, Med. Klinik m. S. Hämatologie, Onkologie, Tumorimmunologie
12200 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Kathrin Rieger, Dr.» Ansprechpartner anzeigen
Marienhospital Düsseldorf, Klinik für Onkologie und Hämatologie, Palliativmedizin
40479 Düsseldorf
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Aristoteles Giagounidis, Prof. Dr.» Ansprechpartner anzeigen
ONCOSEARCH, Institut für Klinische Studien GbR
91052 Erlangen
(Bayern)
GermanyAktiv, nicht rekrutierend» Google-Maps
VK & K Studien GbR, Studienzentrum
84036 Landshut
(Bayern)
GermanyAktiv, nicht rekrutierend» Google-Maps
University Leipzig, Medizinische Klinik und Poliklinik I - Hämatologie und Zelltherapie, Hämostaseologie
04103 Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Uwe Platzbecker, Prof. Dr.» Ansprechpartner anzeigen
Universitätsklinikum Schleswig-Holstein, Klinik für Hämatologie und Onkologie Campus Lübeck
23538 Lübeck
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Friederike Wortmann, Dr.» Ansprechpartner anzeigen
Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik - Hämatologie, Internistische Onkologie und Pneumologie
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Markus Radsak, Prof. Dr.» Ansprechpartner anzeigen
Universitätsklinikum Mannheim, III. Medizinische Klinik - Hämatologie und Onkologie
68167 Mannheim
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Mohamad Jawhar, PD Dr.» Ansprechpartner anzeigen
Klinikum Hochsauerland GmbH, Klinik f. Hämatologie, Onkologie, Palliativmedizin, Stammzelltransplantation
59872 Meschede
(Nordrhein-Westfalen)
GermanyAktiv, nicht rekrutierend» Google-Maps
Klinikum rechts der Isar der TU München III. Medizinische Klinik - Hämatologie und Onkologie
81675 München
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Katharina Götze, Prof. Dr.» Ansprechpartner anzeigen
Friedrich-Ebert-Krankenhaus GmbH, Klinik für Hämatologie, Onkologie und Nephrologie
24534 Neumünster
(Schleswig-Holstein)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Stefan Mahlmann, Dr.» Ansprechpartner anzeigen
Rems-Murr-Kliniken gGmbH, Hämatologie, Onkologie und Palliativmedizin
71364 Winnenden
(Baden-Württemberg)
GermanyAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

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:

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.

Geprüfte Regime

  • CA-4948 (Emavusertib):
    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.

Quelle: ClinicalTrials.gov


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