Clinical trial • Phase III • Oncology

ETOPOSIDE for Acute myeloid leukemia

Phase III trial of ETOPOSIDE for Acute myeloid leukemia.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Acute myeloid leukemia
Trial Stage
Phase III
Drug Modality
Small molecule
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
14-10-2024
First CTIS Authorization Date
12-11-2024

Trial design

Randomised, daunoxome® versus mitoxantrone in course 1 (comparator arm names given; doses/schedules not specified in ctis metadata); fladx versus adxe as second induction course (comparator arm names given; doses/schedules not specified in ctis metadata).-controlled Phase III trial across 41 sites in Belgium, Denmark, Finland and others.

Randomised
Yes
Comparator
DaunoXome® versus Mitoxantrone in course 1 (comparator arm names given; doses/schedules not specified in CTIS metadata); FLADx versus ADxE as second induction course (comparator arm names given; doses/schedules not specified in CTIS metadata).
Biomarker Stratified
True, biomarker: MRD (minimal residual disease); strata/use of MRD threshold (e.g. <0.1% vs >=0.1%) for outcome/risk stratification as described in objectives and primary endpoints.
Target Sample Size
200
Trial Duration For Participant
1825

Eligibility

Recruits 200 paediatric patients.

Pregnancy Exclusion
Positive pregnancy test
Vulnerable Population
The trial explicitly includes children and adolescents (age below 19 years at diagnosis) and has 'isVulnerablePopulationSelected' = true. Written informed consent is required. Age-specific subject information and informed consent/assent forms are provided (examples in the dossier: child and youth ICFs 8-11y, 12-17y, 15-17y, 16y, and parent/guardian consent forms). Documents exist in multiple country/language versions (English, French, Dutch, Danish, Finnish, Spanish, Swedish, Norwegian, Dutch/Netherlands) and specific parent/guardian forms are provided, indicating parental consent for minors and separate youth/child information/assent materials for older children/adolescents.

Inclusion criteria

  • {"criterion_text":"- AML as defined by the diagnostic criteria in the protocol\n- Age below 19 years at time of diagnosis\n- Written informed consent"}

Exclusion criteria

  • {"criterion_text":"- Previous chemotherapy or radiotherapy. This includes patient with secondary AML after previous cancer therapy. They can be treated according to the protocol but will not be included in the study population. Secondary AML has a poorer response to chemotherapy but may benefit from SCT if the procedure can be tolerated.\n- Positive pregnancy test\n- Lactating female or female of childbearing potential not using adequate contraception\n- AML secondary to previous bone marrow failure syndrome.\n- Down syndrome (DS). Patients with myeloid leukaemia of Down syndrome are recommended to be treated according to the international ML-DS protocol. Patients with AML and DS older than 5 years who often lack GATA1 mutation and do not have typical myeloid leukaemia of DS may be treated according to the protocol but will not be included in the study population.\n- Acute promyelocytic leukaemia (APL). These patients are recommended treatment according to the international APL Study.\n- Myelodysplastic syndrome (MDS). These patients are recommended treatment according to EWOG-MDS.\n- Juvenile Myelomonocytic Leukaemia (JMML). These patients are recommended treatment according to EWOG-MDS.\n- Known intolerance to any of the chemotherapeutic drugs in the protocol.\n- Fanconi anemia\n- Major organ failure precluding administration of planned therapy"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The fraction of patients who achieve an MRD level below 0.1%, as quantified by flow cytometry, after the first induction course. (aim 1)\n- The fraction of patients who achieve an MRD level below 0.1%, as quantified by flow cytometry, after the second induction course (aim 2)\n- For patients with fusion genes MRD levels after course 1 and 2 (aim 3)","definition_or_measurement_approach":"MRD quantified by flow cytometry with threshold <0.1% after course 1 and course 2; for patients with fusion genes MRD levels are assessed after courses 1 and 2 (protocol references correlation of MRD measurement by PCR and flow cytometry and prognostic impact of MRD by each method)."}

Secondary endpoints

  • {"endpoint_text":"- Event-free survival and overall survival at five years\n- The median MRD after course 1 and course 2.\n- The rate of CR after one and two induction courses.\n- Cardiac function after one and five years.\n- Frequency of severe adverse events as defined in section 14.2.3 in the protocol, early deaths and deaths in CR","definition_or_measurement_approach":"Event-free survival (EFS) and overall survival (OS) measured at five years; median MRD after course 1 and 2 (measurement method per protocol MRD assays); CR rate after induction courses per protocol response criteria; cardiac function measured at 1 and 5 years (methods per protocol); frequency of severe adverse events as defined in protocol section 14.2.3."}

Recruitment

Planned Sample Size
200
Recruitment Window Months
198
Consent Approach
Written informed consent is required. Age-specific subject information and informed consent/assent forms are provided: child forms (examples: 8-11 years), adolescent forms (examples: 12-17 years, 15-17 years, 16 years), adult forms (18+), and parent/guardian consent forms. Documents are provided in multiple languages across Member States (examples include English, French, Dutch, Danish, Finnish, Spanish, Swedish, Norwegian). Parental/guardian consent forms and youth assent forms are included for minors per country-specific documentation.

Geography

Total Number Of Sites
41
Total Number Of Participants
730

Belgium

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
13-11-2024
Processing Time Days
13
Number Of Sites
6
Number Of Participants
85

Sites

Site Name
Universitair Ziekenhuis Gent
Department Name
Department of Pediatric Hemato-Oncology
Contact Person Name
Barbara De Moerloose
Contact Person Email
Barbara.DeMoerloose@uzgent.be
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Department of Pediatric Hemato-Oncology
Contact Person Name
Bénédicte Brichard
Site Name
UZ Leuven
Department Name
Department of Pediatric Hemato-Oncology
Contact Person Name
Anne Uyttebroeck
Contact Person Email
anne.uyttebroeck@uzleuven.be
Site Name
CHC MontLegia
Department Name
Department of Pediatric Hemato-Oncology
Contact Person Name
Pierre Philippet
Contact Person Email
pierre.philippet@chc.be
Site Name
Association Hospitaliere De Bruxelles Hopital Universitaire Des Enfants Reine Fabiola
Department Name
Department of Pediatric Hemato-Oncology
Contact Person Name
Laurence Dedeken
Site Name
Centre Hospitalier Regional De La Citadelle
Department Name
Department of Pediatric Hemato-Oncology
Contact Person Name
Marie-Françoise Dresse
Contact Person Email
mf.dresse@chuliege.be

Denmark

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
15-11-2024
Processing Time Days
15
Number Of Sites
2
Number Of Participants
35

Sites

Site Name
Region Midtjylland
Department Name
The Research Unit, Department of Paediatrics and Adolescent Medicine
Contact Person Name
Henrik Hasle
Contact Person Email
hasle@dadlnet.dk
Site Name
Rigshospitalet
Department Name
Department of Pediatrics and Adolescent Medicine
Contact Person Name
Marianne Hoffman

Finland

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
13-11-2024
Processing Time Days
13
Number Of Sites
5
Number Of Participants
60

Sites

Site Name
HUS-Yhtymae
Department Name
Department of Children and Adolescents
Contact Person Name
Kirsi Jahnukainen
Contact Person Email
kirsi.jahnukainen@hus.fi
Site Name
Pohjois-Savon hyvinvointialue
Department Name
Department of Pediatrics
Contact Person Name
Kaisa Vepsäläinen
Site Name
Varsinais-Suomen hyvinvointialue
Department Name
Department of Paediatrics and Adolescent Medicine
Contact Person Name
Laura Korhonen
Contact Person Email
laura.korhonen@varha.fi
Site Name
Pohjois-Pohjanmaan hyvinvointialue
Department Name
Department of Pediatrics
Contact Person Name
Riitta Niinimäki
Contact Person Email
riitta.niinimaki@pohde.fi
Site Name
Pirkanmaan hyvinvointialue
Department Name
Department of Children and Adolescents
Contact Person Name
Olli Lohi
Contact Person Email
olli.lohi@pirha.fi

Spain

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
22-11-2024
Processing Time Days
22
Number Of Sites
17
Number Of Participants
325

Sites

Site Name
University Hospital Son Espases
Department Name
Pediatric oncology department
Contact Person Name
Laia Ferrés
Contact Person Email
laia.ferres@ssib.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Pediatric oncology department
Contact Person Name
Laura Murillo
Contact Person Email
laura.murillo@vallhebron.cat
Site Name
Hospital Universitario La Paz
Department Name
Pediatric oncology department
Contact Person Name
Berta González
Contact Person Email
bertagonzalezm@gmail.com
Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Pediatric oncology department
Contact Person Name
J M Pérez Hurtado
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Pediatric oncology department
Contact Person Name
Isabel Badell
Contact Person Email
ibadell@santpau.cat
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Pediatric oncology department
Contact Person Name
Alba Peretó
Contact Person Email
pereto_alb@gva.es
Site Name
Hospital General Universitario Dr. Balmis
Department Name
Pediatric oncology department
Contact Person Name
Maria Tasso
Contact Person Email
tasso_mar@gva.es
Site Name
Complejo Hospitalario Universitario Insular Materno Infantil
Department Name
Pediatric oncology department
Contact Person Name
Antonio Molinés
Contact Person Email
amolhon@gobiernodecanarias.org
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Pediatric oncology department
Contact Person Name
Jose María Fernández
Contact Person Email
fernandez_jma@gva.es
Site Name
Hospital Universitario De Cruces
Department Name
Pediatric oncology department
Contact Person Name
Rosa Adán
Site Name
Hospital Sant Joan De Deu Barcelona
Department Name
Pediatric oncology department
Contact Person Name
Albert Catalá
Contact Person Email
acatala@hsjdbcn.org
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Pediatric oncology department
Contact Person Name
Alexandra Regueiro
Site Name
Hospital Universitario Miguel Servet
Department Name
Pediatric oncology department
Contact Person Name
Yurena Aguilar
Contact Person Email
yurenaaguilar@gmail.com
Site Name
University Clinical Hospital Virgen De La Arrixaca
Department Name
Pediatric oncology department
Contact Person Name
Jose L Fuster
Contact Person Email
josel.fuster@carm
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Pediatric oncology department
Contact Person Name
Cristina Beléndez
Site Name
Hospital Infantil Universitario Nino Jesus
Department Name
Pediatric oncology department
Contact Person Name
Ana Benito
Site Name
Hospital Universitario Regional De Malaga
Department Name
Pediatric oncology department
Contact Person Name
Rosario Prieto
Contact Person Email
draprietobonilla@gmail.com

Sweden

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
12-11-2024
Processing Time Days
12
Number Of Sites
6
Number Of Participants
60

Sites

Site Name
Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vaestra Goetalandsregionen
Department Name
Barncancercentrum, avdelning 1, Drottning Silvias Barn och ungdomssjukhus, 416 85 Göteborg
Contact Person Name
Jonas Abrahamsson
Contact Person Email
jonas.abrahamsson@vgregion.se
Site Name
Region Vaesterbotten
Department Name
Barn 3 Barn- och ungdomscentrum, Norrlands Universitetssjukhus, 901 85 Umeå
Contact Person Name
Ulrika Norén-Nyström
Site Name
Karolinska University Hospital
Department Name
Barnonkologen, Astrid Lindgren sjukhus, Karolinska Universitetssjukhuset, 171 76 Stockholm
Contact Person Name
Karin Belander-Strålin
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Barncancercentrum, avdelning 64, Skånes Universitetssjukhus, 221 85 Lund
Contact Person Name
Cornelis Jan Pronk
Contact Person Email
Cornelis.Pronk@skane.se
Site Name
Region Oestergoetland
Department Name
Barnonkologi, avdelning B153 BOND, H.K.H Universitetssjukhuset Linköping, 5818 85 Linköping
Contact Person Name
Mikael Behrendtz
Site Name
Uppsala University Hospital
Department Name
Barnavdelningen för blod- och tumörsjukdomar 95A, Akademiska Sjukhuset, 751 85 Uppsala
Contact Person Name
Josefine Palle
Contact Person Email
josefine.palle@akademiska.se

Netherlands

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
15-11-2024
Processing Time Days
15
Number Of Sites
1
Number Of Participants
105

Sites

Site Name
Prinses Maxima Centrum voor Kinderoncologie B.V.
Department Name
Department of Hemato-oncology
Contact Person Name
Gertjan Kaspers

Norway

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
14-11-2024
Processing Time Days
14
Number Of Sites
4
Number Of Participants
60

Sites

Site Name
Helse Bergen HF
Department Name
Department of Pediatric and Adolescent Medicine
Contact Person Name
Dorota Wojcik
Site Name
Universitetssykehuset Nord-Norge HF
Department Name
Department of Pediatric and Adolescent Medicine
Contact Person Name
Simon Kranz
Contact Person Email
simon.kranz@unn.no
Site Name
Oslo University Hospital HF
Department Name
Department of Pediatric and Adolescent Medicine
Contact Person Name
Bernward Zeller
Contact Person Email
bzeller@ous-hf.no
Site Name
St. Olavs Hospital HF
Department Name
Department of Pediatric and Adolescent Medicine
Contact Person Name
Bendik Lund
Contact Person Email
bendik.lund@stolav.no

Sponsor

Primary sponsor

Full Name
Vaestra Goetalandsregionen
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Sweden

Third parties

  • {"country":"Denmark","full_name":"Aarhus Universitet","duties_or_roles":"sponsor duties code 1","organisation_type":"Educational Institution"}

Investigational products

Investigational Product Name
ETOPOSIDE
Active Substance
ETOPOSIDE
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
No marketing authorisation
Maximum Dose
150 mg/m2
Investigational Product Name
CYTARABINE
Active Substance
CYTARABINE
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
No marketing authorisation
Maximum Dose
6000 mg/m2
Investigational Product Name
DAUNORUBICIN
Active Substance
DAUNORUBICIN
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
No marketing authorisation
Maximum Dose
60 mg/m2
Investigational Product Name
DAUNORUBICIN HYDROCHLORIDE
Active Substance
DAUNORUBICIN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
No marketing authorisation
Maximum Dose
60 mg/m2
Investigational Product Name
MITOXANTRONE
Active Substance
MITOXANTRONE
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
No marketing authorisation
Maximum Dose
10 mg/m2
Investigational Product Name
FLUDARABINE PHOSPHATE
Active Substance
FLUDARABINE PHOSPHATE
Modality
Small molecule
Routes Of Administration
Intravenous
Route
Intravenous
Authorisation Status
No marketing authorisation
Maximum Dose
30 mg/m2
Combination Treatment
Yes

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