Clinical trial • Phase II • Oncology|Haematology
Cytarabine; Daunorubicin for Myelodysplastic syndrome (higher-risk)|Oligoblastic acute myeloid leukaemia (AML)
Phase II trial of Cytarabine; Daunorubicin for Myelodysplastic syndrome (higher-risk)|Oligoblastic acute myeloid leukaemia (AML).
Overview
- Trial Therapeutic Area
- Oncology|Haematology
- Trial Disease
- Myelodysplastic syndrome (higher-risk)|Oligoblastic acute myeloid leukaemia (AML)
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 19-09-2024
- First CTIS Authorization Date
- 20-10-2024
Trial design
Conventional care regimens (CCR) as comparator: Daunorubicin hydrochloride (intravenous; maxDailyDoseAmount 60 mg/m2), Cytarabine (intravenous; maxDailyDoseAmount 1500 mg/m2), Azacitidine (subcutaneous; maxDailyDoseAmount 75 mg/m2) — specific regimen/schedule not detailed in the available data.-controlled Phase II trial across 26 sites in Austria, Germany.
- Comparator
- Conventional care regimens (CCR) as comparator: Daunorubicin hydrochloride (intravenous; maxDailyDoseAmount 60 mg/m2), Cytarabine (intravenous; maxDailyDoseAmount 1500 mg/m2), Azacitidine (subcutaneous; maxDailyDoseAmount 75 mg/m2) — specific regimen/schedule not detailed in the available data.
- Target Sample Size
- 150
Eligibility
Recruits 150 Vulnerable population is selected. Trial enrols adults only (18-75) and requires signed informed consent. Participants with any condition preventing obtaining informed consent are excluded. Subject information and informed consent forms for adults are available (German); optional biobanking consent and pregnancy-related partner/participant ICFs are documented. No paediatric assent procedures (paediatrics excluded)..
- Pregnancy Exclusion
- Female patients who are pregnant or lactating.
- Vulnerable Population
- Vulnerable population is selected. Trial enrols adults only (18-75) and requires signed informed consent. Participants with any condition preventing obtaining informed consent are excluded. Subject information and informed consent forms for adults are available (German); optional biobanking consent and pregnancy-related partner/participant ICFs are documented. No paediatric assent procedures (paediatrics excluded).
Inclusion criteria
- {"criterion_text":"- Adult patients (irrespective of sex), 18-75 years of age\n- Contraception: - Female subjects of childbearing potential† must agree to use a medically acceptable method of contraception for at least 2 months prior to the first dose of CPX-351 and consent of female patients to use a medically acceptable method of contraception throughout the entire study period and for 6 months following the last dose of CPX-351; Male patients must be willing to refrain from sperm donation for 6 months following the last dose of CPX-351 and must use adequate contraception throughout the entire study period and for 6 months following the last dose of CPX-351\n- Diagnosis of high risk MDS including oligoblastic non-proliferative (WBC <13 Gpt/l) AML up to 29% of bone marrow blasts\n- Bone marrow blasts ≥ 5% (central morphology Düsseldorf)\n- IPSS score intermediate or high\n- alloHCT intended within the next 6 months\n- ECOG performance status of 0 or 1\n- Signed informed consent\n- Laboratory values fulfilling all of the following: Serum creatinine < 2.0 mg/dL; Serum total bilirubin < 2.0 mg/dL; Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN\n- Cardiac ejection fraction (LVEF) ≥ 50% by echocardiography"}
Exclusion criteria
- {"criterion_text":"- Patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.\n- WHO-2016 defined AML entities: AML with t(15;17), PMLRARA; AML with t(8;21), RUNX1-RUNX1T1, AML with inv(16)/t(16;16), CBFβ-MYH11; AML with BCR-ABL1, AML with biallelic CEBPA mutation; AML with mutated FLT3 or NPM1.\n- Clinical evidence of active CNS leukaemia.\n- Patients with a “currently active” second malignancy other than non-melanoma skin cancers. Patients are not considered to have a “currently active” malignancy if they have completed therapy more than 2 years ago and are disease free.\n- Any major surgery or radiation therapy within four weeks prior screening.\n- Patients with prior treatment of either CPX-351, hypomethylating agents, cytarabine or intensive chemotherapy for high-risk MDS or AML.\n- Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).\n- Recent (< 30 days) or planned live vaccinations during the clinical trial.\n- Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent.\n- Creatinine clearance < 30 ml/min.\n- Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥ 72 hrs.\n- Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values).\n- Hypersensitivity to cytarabine, daunorubicin or liposomal products.\n- History of Wilson’s disease or other copper-metabolism disorder, unless the therapy outweighs the risks.\n- Female patients who are pregnant or lactating."}
Endpoints
Primary endpoints
- {"endpoint_text":"- EFS with a data cut off date of September 2025","definition_or_measurement_approach":"Event-free survival (EFS) comparing CPX-351 vs. conventional care regimens (CCR) prior to allogeneic HCT; data cut-off date September 2025"}
Secondary endpoints
- {"endpoint_text":"- Best and overall response rate according to AML-ELN and MDS-IWG criteria","definition_or_measurement_approach":"Response assessed according to AML-ELN and MDS-IWG criteria"}
- {"endpoint_text":"- Toxicity as measured by NCI CTCAE v5.0","definition_or_measurement_approach":"Adverse event grading per NCI CTCAE version 5.0"}
- {"endpoint_text":"- Proportion of patients proceeding to alloHCT","definition_or_measurement_approach":"Proportion of randomized patients who proceed to allogeneic haematopoietic cell transplantation"}
- {"endpoint_text":"- MRD assessed at all times of BM puncture","definition_or_measurement_approach":"Minimal residual disease (MRD) assessment at each bone marrow puncture timepoint"}
- {"endpoint_text":"- Quality of life as measured by EORTC-QLQ30 supplemented by information on self-assessed concomitant diseases and demographics upon inclusion and at EOT (i.e. before alloHCT, if applicable)","definition_or_measurement_approach":"Quality of life measured using EORTC QLQ-C30 questionnaire and supplementary self-assessed comorbidity and demographic information at baseline and end of treatment"}
- {"endpoint_text":"- Key Secondary Endpoint: OS with a data cut-off dates of September 2025 for interim and September 2026 for final","definition_or_measurement_approach":"Overall survival (OS) with interim data cut-off September 2025 and final cut-off September 2026"}
Recruitment
- Planned Sample Size
- 150
- Recruitment Window Months
- 89
- Consent Approach
- Signed informed consent is required from adult participants (18-75). Subject information and informed consent forms for adults are available (documents titled L1_SIS and ICF adults; German language indicated). Optional biobanking consent and pregnancy/partner-specific ICFs are provided. No paediatric assent procedures (paediatric subjects excluded).
Geography
- Total Number Of Sites
- 26
- Total Number Of Participants
- 150
Austria
- Latest Decision Or Authorization Date
- 20-10-2024
- Number Of Sites
- 1
- Number Of Participants
- 20
Sites
- Site Name
- Ordensklinikum Linz GmbH
- Department Name
- Ordensklinikum Linz Elisabethinen GmbH
- Contact Person Name
- Sigrid Machherndl-Spandl
- Contact Person Email
- ZentrumKlinischeStudien@ordensklinikum.at
Germany
- Latest Decision Or Authorization Date
- 24-10-2024
- Number Of Sites
- 25
- Number Of Participants
- 130
Sites
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Innere Medizin III
- Contact Person Name
- Katharina Götze
- Contact Person Email
- katharina.goetze@mri.tum.de
- Site Name
- Universitaetsklinikum Aachen AöR
- Department Name
- Uniklinik RWTH Aachen, Medizinische Klinik IV
- Contact Person Name
- Martina Margit Crysandt
- Contact Person Email
- mcrysandt@ukaachen.de
- Site Name
- Robert Bosch Krankenhaus GmbH
- Department Name
- Robert-Bosch-Krankenhaus Stuttgart, Abteilung Hämatologie, Onkologie, Studieneinheit ZIM2
- Contact Person Name
- Martin Kaufmann
- Contact Person Email
- martin.kaufmann@rbk.de
- Site Name
- Universitaetsklinikum Ulm AöR
- Department Name
- Universitätsklinikum Ulm Klinik für Innere Medizin III AMLSG-Sekretariat
- Contact Person Name
- Hartmut Döhner
- Contact Person Email
- hartmut.doehner@uniklinik-ulm.de
- Site Name
- Universitaetsklinikum Mannheim GmbH
- Department Name
- Universitätsmedizin Mannheim III. Medizinische Klinik
- Contact Person Name
- Stefan Klein
- Contact Person Email
- stefan.klein@umm.de
- Site Name
- Klinikum Chemnitz gGmbH
- Department Name
- Klinikum Chemnitz-gGmbH Klinik für Innere Medizin III
- Contact Person Name
- Mathias Hänel
- Contact Person Email
- m.haenel@skc.de
- Site Name
- Universitaetsklinikum Duesseldorf AöR
- Department Name
- Universitätsklinikum Düsseldorf
- Contact Person Name
- Ulrich Germing
- Contact Person Email
- germing@med.uni-duesseldorf.de
- Site Name
- Universitaetsklinikum Carl Gustav Carus Dresden AöR
- Department Name
- Universitätsklinikum Carl Gustav Carus Dresden an der TU Dresden, Medizinische Klinik I, Hämatologie
- Contact Person Name
- Christoph Röllig
- Contact Person Email
- Christoph.Roellig@uniklinikum-dresden.de
- Site Name
- HELIOS Klinikum Berlin-Buch GmbH
- Department Name
- Klinik für Hämatologie und Stammzelltransplantation
- Contact Person Name
- Judith Niederland
- Contact Person Email
- judith.niederland@helios-gesundheit.de
- Site Name
- Universitaetsklinikum Leipzig AöR
- Department Name
- Hematology and Cell Therapy, University Hospital Leipzig
- Contact Person Name
- Madlen Jentzsch
- Contact Person Email
- madlen.jentzsch@medizin.uni-leipzig.de
- Site Name
- Goethe University Frankfurt
- Department Name
- Universitätsklinikum Frankfurt, Medizinische Klinik II
- Contact Person Name
- Gesine Bug
- Contact Person Email
- bug@em.uni-frankfurt.de
- Site Name
- Universitaetsklinikum Halle (Saale) AöR
- Department Name
- Universitätsklinikum Halle, Klinik und Poliklinik für Innere Medizin IV
- Contact Person Name
- Christine Dierks
- Contact Person Email
- christine.dierks@uk-halle.de
- Site Name
- University Hospital Cologne AöR
- Department Name
- Universitätsklinikum Köln, Klinik I für Innere Medizin
- Contact Person Name
- Christof Scheid
- Contact Person Email
- christoph.scheid@uk-koeln.de
- Site Name
- Universitaetsklinikum Augsburg
- Department Name
- Universitätsklinikum Augsburg, II. Medizinische Klinik-Hämatologie, Onkologie
- Contact Person Name
- Andreas Rank
- Contact Person Email
- andreas.rank@uk-augsburg.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Charité-Universitätsmedizin Berlin, Medizinische Klinik, CBF
- Contact Person Name
- Jan Krönke
- Contact Person Email
- jan.kroenke@charite.de
- Site Name
- Medizinische Hochschule Hannover
- Department Name
- MHH, Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
- Contact Person Name
- Felicitas Thol
- Contact Person Email
- thol.felicitas@mh-hannover.de
- Site Name
- Universitaetsklinikum Bonn AöR
- Department Name
- Universitätsklinikum Bonn (UKB) Med Klinik III, Abt. für Hämatologie, Onkologie, Rheumatologie
- Contact Person Name
- Tobias Holderried
- Contact Person Email
- tobias.holderried@ukbonn.de
- Site Name
- Universitaetsklinikum Jena KöR
- Department Name
- Universitätsklinikum Jena Klinik für Innere Medizin II
- Contact Person Name
- Inken Hilgendorf
- Contact Person Email
- Inken.Hilgendorf@med.uni-jena.de
- Site Name
- Rostock University Medical Center
- Department Name
- Universitätsmedizin Rostock Klinik III, Zentrum für Innere Medizin
- Contact Person Name
- Christian Junghanss
- Contact Person Email
- christian.junghanss@med.uni-rostock.de
- Site Name
- Gemeinschaftsklinikum Mittelrhein gGmbH
- Department Name
- Gemeinschaftsklinikum Mittelrhein gGmbH Ev. Stift St. Martin Klinik für Innere Med, Studienzentrum
- Contact Person Name
- Dirk Niemann
- Contact Person Email
- dirk.niemann@gk.de
- Site Name
- Universitaetsklinikum Tuebingen AöR
- Department Name
- Universitätsklinikum Tübingen Medizinische Klinik Abteilung Innere Medizin II
- Contact Person Name
- Wolfgang Bethge
- Contact Person Email
- wolfgang.bethge@med.uni-tuebingen.de
- Site Name
- Klinikum Nuernberg
- Department Name
- Klinikum Nürnberg, Klinik für Onkologie und Hämatologie, Einheit für Knochenmarktransplantation
- Contact Person Name
- Kerstin Schäfer-Eckhart
- Contact Person Email
- schaefer@klinikum-nuernberg.de
- Site Name
- Klinikum Frankfurt (Oder) GmbH
- Department Name
- Klinikum Frankfurt(Oder) GmbH, Medizinische Klinik I
- Contact Person Name
- Olaf Hopfer
- Contact Person Email
- innere@klinikumffo.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Universitätsklinikum Essen, Klinik für Hämatologie und Stammzelltransplantation
- Contact Person Name
- Thomas Schröder
- Contact Person Email
- Thomas.Schroeder@uk-essen.de
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- Universitätsklinikum Heidelberg, Medizinische Klinik und Poliklinik V
- Contact Person Name
- Tim Sauer
- Contact Person Email
- tim.sauer@med.uni-heidelberg.de
Sponsor
Primary sponsor
- Full Name
- GWT-Tud GmbH
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Germany
Third parties
- {"country":"Germany","full_name":"Universitaetsklinikum Leipzig AöR","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Germany","full_name":"National Center For Tumor Diseases (NCT) Heidelberg","duties_or_roles":"code 10","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Universitaetsklinikum Duesseldorf AöR","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Germany","full_name":"Universitaetsklinikum Leipzig AöR","duties_or_roles":"Biobanking (code 15)","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"code 14","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Universitaet Leipzig","duties_or_roles":"code 1, code 6, code 8","organisation_type":"Educational Institution"}
Investigational products
- Investigational Product Name
- Vyxeos Liposomal 44 mg/100 mg powder for concentrate for solution for infusion.
- Active Substance
- Cytarabine; Daunorubicin
- Modality
- Small molecule
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Authorisation Status
- EU/1/18/1308/001
- Maximum Dose
- 100 U unit(s)
- Investigational Product Name
- DAUNORUBICIN HYDROCHLORIDE
- Active Substance
- Daunorubicin hydrochloride
- Modality
- Small molecule
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Maximum Dose
- 60 mg/m2 milligram(s)/square meter
- Investigational Product Name
- CYTARABINE
- Active Substance
- Cytarabine
- Modality
- Small molecule
- Routes Of Administration
- Intravenous
- Route
- Intravenous
- Maximum Dose
- 1500 mg/m2 milligram(s)/square meter
- Investigational Product Name
- AZACITIDINE
- Active Substance
- Azacitidine
- Modality
- Small molecule
- Routes Of Administration
- Subcutaneous injection
- Route
- Subcutaneous
- Maximum Dose
- 75 mg/m2 milligram(s)/square meter
- Combination Treatment
- Yes
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