Clinical trial • Phase II • Oncology|Haematology

VENETOCLAX for Acute myeloid leukemia

Phase II trial of VENETOCLAX for Acute myeloid leukemia.

Overview

Trial Therapeutic Area
Oncology|Haematology
Trial Disease
Acute myeloid leukemia
Trial Stage
Phase II
Drug Modality
Small molecule|ADC
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
14-10-2024
First CTIS Authorization Date
23-10-2024

Trial design

GEMTUZUMAB OZOGAMICIN — intravenous; max daily dose 3 mg/m2 (as listed). DAUNORUBICIN HYDROCHLORIDE — intravenous; max daily dose 60 mg/m2 (as listed). MITOXANTRONE — intravenous; max daily dose 10 mg/m2 (as listed). CYTARABINE — intravenous; max daily dose 3000 mg/m2 (as listed). (Collectively described as standard intensive chemotherapy / comparator agents in the application.)-controlled Phase II trial across 25 sites in Germany.

Comparator
GEMTUZUMAB OZOGAMICIN — intravenous; max daily dose 3 mg/m2 (as listed). DAUNORUBICIN HYDROCHLORIDE — intravenous; max daily dose 60 mg/m2 (as listed). MITOXANTRONE — intravenous; max daily dose 10 mg/m2 (as listed). CYTARABINE — intravenous; max daily dose 3000 mg/m2 (as listed). (Collectively described as standard intensive chemotherapy / comparator agents in the application.)
Target Sample Size
146

Eligibility

Recruits 146 Vulnerable population selected (isVulnerablePopulationSelected = true). Informed consent is required: 'Signed informed consent' and 'Ability to understand and the willingness to sign a written informed consent.' No details on assent or proxy consent are provided in the available record..

Pregnancy Exclusion
Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours before first dose of study drug.
Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected = true). Informed consent is required: 'Signed informed consent' and 'Ability to understand and the willingness to sign a written informed consent.' No details on assent or proxy consent are provided in the available record.

Inclusion criteria

  • {"criterion_text":"- Signed informed consent\n- Newly diagnosed CD33-positive AML with NPM1 mutation according to WHO criteria\n- Age 18-70 years\n- Fit for intensive chemotherapy, defined by: 1. ECOG 0-2 2. Adequate hepatic function: ALAT/ASAT/Bilirubin ≤ 2.5 x ULN unless considered due to leukemic organ involvement (Note: Subjects with Gilbert's Syndrome may have a bilirubin > 2.5 × ULN per discussion between the investigator and Coordinating investigator.) 3. Adequate renal function assessed by serum creatinine ≤ 1.5x ULN OR creatinine clearance (by Cockcroft Gault formula) ≥ 50 mL/min\n- WBC < 25 x 109/L (<25,000/µL) (Note: Prior hydroxyurea is permitted to meet this criterion.)\n- Ability to understand and the willingness to sign a written informed consent.\n- Male subjects must agree to refrain from unprotected sex and sperm donation from time point of signing the informed consent until 7 months after the last dose of study drug.\n- Women of childbearing potential must have a negative serum pregnancy test performed within 72 hours before first dose of study drug."}

Exclusion criteria

  • {"criterion_text":"- Activating FLT3 mutation\n- Known positivity for human immunodeficiency virus (HIV), and history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection (i.e. PCR undetectable viral load for hepatitis).\n- Inability to swallow oral medications\n- Any malabsorption condition\n- Cardiovascular disability status of New York Heart Association (NYHA) Class ≥ 2, unstable coronary artery disease (MI more than 6 months prior to study entry is permitted); serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy (Note: Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain).\n- Relapsed or refractory AML\n- AML after antecedent myelodysplasia (MDS) with prior cytotoxic treatment\n- Prior history of malignancy, other than MDS, unless the subject has been free of the disease for equal to or greater than 1 year prior to start of study treatment (exceptions are basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or of the breast, incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis clinical staging system))\n- Previous treatment with HMA or venetoclax\n- Previous treatment for AML except hydroxyurea\n- Cumulative previous exposure to anthracyclines of > 200 mg/m2 doxorubicin equivalents\n- CNS involvement or extramedullary disease only\n- Known hypersensitivity to excipients of the preparation or any agent given in association with this study including venetoclax, azacitidine, cytarabine, daunorubicin, gemtuzumab-ozogamicin, or mitoxantrone"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Modified Event-free survival (mEFS)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Event is defined as: 1. Failure to achieve a CR/CRi/CRh after maximum of two induction cycles in the control arm (SOC) or three induction cycles in the investigational arm (VEN+AZA), i.e. primary induction failure","definition_or_measurement_approach":"Defines one component of the mEFS event (primary induction failure after specified induction cycles per arm)."}
  • {"endpoint_text":"- Event is defined as: 2. Hematologic relapse after previous CR/CRi/CRh","definition_or_measurement_approach":"Defines relapse component of the mEFS event."}
  • {"endpoint_text":"- Event is defined as: 3. Molecular failure, defined as either: 3.1 Molecular progression, defined as confirmed ≥ 1 log10 increase of NPM1 MRD level in any two samples in a patient without prior MRD negativity or 3.2 Molecular relapse after previous MRD negativity, defined as confirmed ≥ 1 log10 between two consecutive positive samples in a patient who was previously tested as MRD negative","definition_or_measurement_approach":"Defines molecular failure component of mEFS measured by NPM1 MRD level changes (real-time PCR), with specified ≥1 log10 thresholds and confirmation across samples."}
  • {"endpoint_text":"- Event is defined as: 4. Death","definition_or_measurement_approach":"Death as an event contributing to mEFS."}

Secondary endpoints

  • {"endpoint_text":"- Cumulative occurrence of grade 3 and 4 adverse events (tolerability)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Rate of morphologic CR and CR/CRi/CRh with MRD negativity","definition_or_measurement_approach":""}
  • {"endpoint_text":"- MRD as detected by MFC and MRD kinetics in NPM1 real-time PCR","definition_or_measurement_approach":"MRD assessed by MFC and NPM1 RT-PCR kinetics."}
  • {"endpoint_text":"- Rate of molecular response and molecular persistence","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Relapse-free survival and overall survival","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Early mortality (14 d, 30 d, 60 d from start of induction)","definition_or_measurement_approach":"Timepoint-specific mortality rates measured at 14, 30, and 60 days from start of induction."}
  • {"endpoint_text":"- Change in Health-related quality of life (QoL)","definition_or_measurement_approach":""}
  • {"endpoint_text":"- Cumulative health-care resource use at 12 and 24 months","definition_or_measurement_approach":"Health-care resource use aggregated at 12 and 24 months."}

Recruitment

Planned Sample Size
146
Recruitment Window Months
44
Consent Approach
Signed informed consent required from participant. Eligibility criteria include 'Signed informed consent' and 'Ability to understand and the willingness to sign a written informed consent.' Subject information and informed consent form documents are listed (main study, translational research, pregnant partner), but languages and assent/proxy consent procedures are not specified in the available record.

Geography

Total Number Of Sites
25
Total Number Of Participants
146

Germany

Earliest CTIS Part Ii Submission Date
21-10-2024
Latest Decision Or Authorization Date
22-04-2026
Processing Time Days
548
Number Of Sites
25
Number Of Participants
146

Sites

Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Klinik für Innere Medizin II; Hämatologie und Onkologie
Principal Investigator Name
Lars Fransecky
Principal Investigator Email
Lars.Fransecky@uksh.de
Contact Person Name
Lars Fransecky
Contact Person Email
Lars.Fransecky@uksh.de
Site Name
Barmherzige Brueder gemeinnuetzige Krankenhaus GmbH
Department Name
Klinik für Onkologie und Hämatologie;
Principal Investigator Name
Nadia Maguire
Principal Investigator Email
nadia.maguire@barmherzige-regensburg.de
Contact Person Name
Nadia Maguire
Site Name
Technische Universitaet Dresden
Department Name
Medizinische Klinik und Poliklinik I; Hämatologie, Zelltherapie und Medizinische Onkologie
Principal Investigator Name
Christoph Röllig
Principal Investigator Email
christoph.roellig@ukdd.de
Contact Person Name
Christoph Röllig
Contact Person Email
christoph.roellig@ukdd.de
Site Name
Klinikum Nuernberg
Department Name
Klinik für Innere Medizin 5; Onkologie und Hämatologie
Principal Investigator Name
Kerstin Schäfer-Eckhart
Contact Person Name
Kerstin Schäfer-Eckhart
Site Name
Sozialstiftung Bamberg
Department Name
Medizinische Klinik V; Hämatologie und Internistische Onkologie
Principal Investigator Name
Alexander Porst
Principal Investigator Email
alexander.porst@sozialstiftung-bamberg.de
Contact Person Name
Alexander Porst
Site Name
Robert Bosch Krankenhaus GmbH
Department Name
Hämatologie, Onkologie und Palliativmedizin
Principal Investigator Name
Martin Kaufmann
Principal Investigator Email
martin.kaufmann@rbk.de
Contact Person Name
Martin Kaufmann
Contact Person Email
martin.kaufmann@rbk.de
Site Name
Universitaet Leipzig
Department Name
Klinik und Poliklinik für Hämatologie, Zelltherapie, Hämostaseologie und Infektiologie;
Principal Investigator Name
Klaus Metzeler
Principal Investigator Email
klaus.metzeler@medizin.uni-leipzig.de
Contact Person Name
Klaus Metzeler
Site Name
Klinikum Bielefeld gGmbH
Department Name
Klinik für Hämatologie, Onkologie, Palliativmedizin und Stammzelltherapie
Principal Investigator Name
Kai Wegehenkel
Principal Investigator Email
kai.wegehenkel@klinikumbielefeld.de
Contact Person Name
Kai Wegehenkel
Site Name
Heidelberg University
Department Name
Universitätsmedizin Mannheim; III. Medizinische Klinik
Principal Investigator Name
Stefan Klein
Principal Investigator Email
stefan.klein@umm.de
Contact Person Name
Stefan Klein
Contact Person Email
stefan.klein@umm.de
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation (Med. Klin. IV)
Principal Investigator Name
Martina Crysandt
Principal Investigator Email
mcrysandt@ukaachen.de
Contact Person Name
Martina Crysandt
Contact Person Email
mcrysandt@ukaachen.de
Site Name
St. Bernward Krankenhaus GmbH
Department Name
Medizinische Klinik II; MVZ für Onkologie
Principal Investigator Name
Christian Könecke
Principal Investigator Email
c.koenecke@bernward-khs.de
Contact Person Name
Christian Könecke
Contact Person Email
c.koenecke@bernward-khs.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Klinik für Hämatologie und Stammzelltransplantation
Principal Investigator Name
Thomas Schroeder
Principal Investigator Email
thomas.schroeder@uk-essen.de
Contact Person Name
Thomas Schroeder
Contact Person Email
thomas.schroeder@uk-essen.de
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Campus Großhadern; Medizinische Klinik und Poliklinik III; Onkologie und Hämatologie
Principal Investigator Name
Veit Bücklein
Principal Investigator Email
veit.buecklein@med.uni-muenchen.de
Contact Person Name
Veit Bücklein
Site Name
Universitaetsklinikum Erlangen AöR
Department Name
Medizinische Klinik 5; Hämatologie und Internistische Onkologie
Principal Investigator Name
Heidi Waibel
Principal Investigator Email
heidi.waibel@uk-erlangen.de
Contact Person Name
Heidi Waibel
Contact Person Email
heidi.waibel@uk-erlangen.de
Site Name
Klinikum Chemnitz gGmbH
Department Name
Klinik für Innere Medizin III
Principal Investigator Name
Mathias Hänel
Principal Investigator Email
m.haenel@skc.de
Contact Person Name
Mathias Hänel
Contact Person Email
m.haenel@skc.de
Site Name
University Hospital Cologne AöR
Department Name
Klinik I für Innere Medizin; CIO
Principal Investigator Name
Lukas Frenzel
Principal Investigator Email
lukas.frenzel@uk-koeln.de
Contact Person Name
Lukas Frenzel
Contact Person Email
lukas.frenzel@uk-koeln.de
Site Name
Martin-Luther-Universitaet Halle-Wittenberg
Department Name
Universitätsklinik und Poliklinik für Innere Medizin IV; Hämatologie und Onkologie
Principal Investigator Name
Judith Schaffrath
Principal Investigator Email
judith.schaffrath@uk-halle.de
Contact Person Name
Judith Schaffrath
Contact Person Email
judith.schaffrath@uk-halle.de
Site Name
Universitaetsklinikum Duesseldorf AöR
Department Name
Klinik für Hämatologie, Onkologie und Klinische Immunologie;
Principal Investigator Name
Paul Jäger
Contact Person Name
Paul Jäger
Site Name
Rotkreuzklinikum Muenchen gGmbH
Department Name
Innere Medizin III; Hämatologie und Onkologie
Principal Investigator Name
Marcus Hentrich
Principal Investigator Email
marcus.hentrich@swmbrk.de
Contact Person Name
Marcus Hentrich
Contact Person Email
marcus.hentrich@swmbrk.de
Site Name
HELIOS Dr. Horst Schmidt Kliniken Wiesbaden GmbH
Department Name
Innere Medizin III; Hämatologie, Onkologie, Palliativmedizin
Principal Investigator Name
Bodo Manning
Principal Investigator Email
bodo.manning@helios-gesundheit.de
Contact Person Name
Bodo Manning
Site Name
Goethe University Frankfurt
Department Name
Medizinische Klinik II; Hämatologie/Onkologie
Principal Investigator Name
Björn Steffen
Principal Investigator Email
steffen@em.uni-frankfurt.de
Contact Person Name
Björn Steffen
Contact Person Email
steffen@em.uni-frankfurt.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Innere Medizin V; Hämatologie, Onkologie und Rheumatologie
Principal Investigator Name
Tim Sauer
Principal Investigator Email
tim.sauer@med.uni-heidelberg.de
Contact Person Name
Tim Sauer
Site Name
Universitaetsklinikum Augsburg
Department Name
III. Medizinische Klinik; Hämatologie und Internistische Onkologie
Principal Investigator Name
Christoph Schmid
Principal Investigator Email
Christoph.Schmid@klinikum-augsburg.de
Contact Person Name
Christoph Schmid
Site Name
Universitaet Muenster
Department Name
Medizinische Klinik A; Hämatologie, Hämostaseologie, Onkologie und Pneumologie
Principal Investigator Name
Christoph Schliemann
Principal Investigator Email
Christoph.Schliemann@ukmuenster.de
Contact Person Name
Christoph Schliemann
Site Name
Philipps-Universitaet Marburg
Department Name
Klinik für Innere Medizin; Hämatologie, Onkologie und Immunologie
Principal Investigator Name
Andreas Burchert
Principal Investigator Email
burchert@staff.uni-marburg.de
Contact Person Name
Andreas Burchert
Contact Person Email
burchert@staff.uni-marburg.de

Sponsor

Primary sponsor

Full Name
Technische Universitaet Dresden
Organisation Type
Educational Institution
Country Of Registered Address
Germany

Third parties

  • {"country":"Germany","full_name":"AbbVie Deutschland GmbH & Co. KG","duties_or_roles":"Source of monetary support","organisation_type":"Commercial / Pharmaceutical company"}

Investigational products

Investigational Product Name
Venetoclax
Active Substance
VENETOCLAX
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
Oral
Authorisation Status
Authorised
Orphan Designation
Yes
Maximum Dose
400 mg
Investigational Product Name
AZACITIDINE
Active Substance
AZACITIDINE
Modality
Small molecule
Routes Of Administration
SUBCUTANEOUS
Route
Subcutaneous
Authorisation Status
Not authorised
Orphan Designation
Yes
Maximum Dose
75 mg/m2
Investigational Product Name
CYTARABINE
Active Substance
CYTARABINE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Not authorised
Maximum Dose
3000 mg/m2
Investigational Product Name
GEMTUZUMAB OZOGAMICIN
Active Substance
GEMTUZUMAB OZOGAMICIN
Modality
ADC
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Not authorised
Orphan Designation
Yes
Maximum Dose
3 mg/m2
Investigational Product Name
DAUNORUBICIN HYDROCHLORIDE
Active Substance
DAUNORUBICIN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Not authorised
Orphan Designation
Yes
Maximum Dose
60 mg/m2
Investigational Product Name
MITOXANTRONE
Active Substance
MITOXANTRONE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Not authorised
Maximum Dose
10 mg/m2
Combination Treatment
Yes

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