Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
650
Countries
7
Sites
78
mature aggressive B-cell lymphoma and leukemia in children and adolescents
Analyzing in pediatric patients (pts) •the event-free survival (EFS) in pts with very limited B-NHL (R1 and R2 stage I and II) substituting anthracyclines by the rituximab window (R) without compromising survival rates. •the EFS in pts with limited B-NHL (R2 stage III) randomly assigned to receive R plus standard chemo…
Key facts
- Sponsor
- Universitaetsklinikum Muenster AöR
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 12 Jul 2017 → ongoing
- Decision date (initial)
- 2023-10-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2023-505509-18-00
- EudraCT number
- 2013-003253-21
- ClinicalTrials.gov
- NCT03206671
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Pharmacogenetic, Therapy, Efficacy, Safety
Analyzing in pediatric patients (pts)
•the event-free survival (EFS) in pts with very limited B-NHL (R1 and R2
stage I and II) substituting anthracyclines by the rituximab window (R)
without compromising survival rates.
•the EFS in pts with limited B-NHL (R2 stage III) randomly assigned to
receive R plus standard chemotherapy (S-CTX) or S-CTX without R.
•the EFS and the immune reconstitution (recovery of CD19+ B-cells, IR)
in pts with advanced B-NHL/B-AL (R3 and R4 incl. R4 CNS+) treated
with BFM-type CTX and randomly assigned schedules of one versus
seven doses rituximab. One dose rituximab = R plus S-CTX. Seven doses
rituximab = R plus S-CTX with additional six doses of rituximab added to
the first four courses of CTX. It will be tested whether EFS can be
improved by adding rituximab and whether one dose rituximab is
sufficient to achieve the intended improvement of EFS. In addition, the
IR will be analyzed comparing the effect of the two regimens of
rituximab added to S-CTX.
Secondary objectives 1
- Analyzing •Event-free survival, overall survival and immune reconstitution for subgroups: histology; CNS status; gender; age: <10 years (y), 10-14 y, >14 y; risk group: R3 versus R4; CD19+ count and/or immunoglobulin (Ig) level prior treatment; Ig substitution; initial performance; response after rituximab window R, after prephase V, after 2nd course; study groups/national groups: BFM versus NOPHO; national groups; and others •additional parameters for immune reconstitution (IR): lymphocyte subpopulations, Ig levels and grade III/V infections at 6, 12, 18 and 24 months after start of treatment continued 6-monthly until normalization comparing the randomized arms in R3/R4 patients (pts) and evaluating IR in R1/R2 pts. The rate of pts who achieve sufficient titers after vaccination one year after start of treatment will be analyzed •the effect of one versus seven doses of rituximab on the rate of AE and SAE profile of the randomized arms in R3/R4 pts
Conditions and MedDRA coding
mature aggressive B-cell lymphoma and leukemia in children and adolescents
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | SOC | 10005329 | Blood and lymphatic system disorders | 3 |
| 20.0 | HLGT | 10025320 | Lymphomas non-Hodgkin's B-cell | 10029104 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- newly diagnosed, histological or cytological and immunological proven aggressive mature B-cell Non-Hodgkin lymphoma including Burkitt lymphoma (BL), Burkitt leukemia (B-AL), diffuse large B-cell lymphoma (DLBCL), or mature B-cell NHL not further classified according to current WHO classification. For rare subtypes (e.g. primary mediastinal large BNHL, PMLBL double hit lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements), consultation of the study center is recommended
- availability of slides/blocks for reference pathology and international pathology panel (except in cases with immunological and cytomorphological assurance of diagnosis)
- age at diagnosis < 18 years
- diagnostics and treatment in one of the participating centers of the trial
- no previous chemotherapy, no previous lymphoma-directed treatment. No application of steroids for more than two days during the last month
- adequate hepatic, renal and cardiac function, except if alteration is due to lymphoma Infiltration. Please contact the study center in case of unclear cases
- signed informed consent of patient and or parents/guardians for treatment according to the protocol, participation and transfer of data
- follow-up of at least two years after initial diagnosis is expected
- certificate of vaccination against hepatitis B or negative serology, defined as - evidence of immunization with HBs-antigen negative, anti-HBs positive and anti-HBc negative or - negative hepatitis B serology with HBs-antigen negative, anti- HBs and anti-HBc negative E.
Exclusion criteria 8
- patients with insufficient work up not allowing a correct stratification into the risk groups
- B-cell neoplasia as second malignancy
- any other medical, psychiatric, or social condition prohibiting treatment according to the protocol (e.g. previous malignancy, prior organ transplant, HIV infection or AIDS or severe immunodeficiency, etc.)
- participation within a different trial for treatment of B-cell malignancies and/or concurrent treatment within any other clinical trial. Exceptions to this are the NHL-BFM Registry 2012 and trials with different endpoints, involving aspects of supportive treatment which can run parallel to B-NHL 2013 without influencing the outcome of this trial e.g. trials on antiemetics, antibiotics, strategies for psychosocial support etc.
- overt hepatitis B or history of hepatitis B
- hypersensitivity to rituximab or to murine proteins, or to any of the other excipients of the Investigational Medicinal Product or to ingredients of other IMPs
- lack of CD20 expression of the lymphoma cells
- pregnancy and lactation
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 3
- For R1/R2- patients with stage I+II the primary endpoint is event-free survival (EFS_T) defined as time from start of treatment up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.
- For R2 patients with stage III disease (the 1st randomized study question) the primary endpoint is event-free survival (EFS_R) defined as time from randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.
- R3/R4 patients(pts)(2nd randomized question): 1.Event-free survival(EFS_T/EFS_R):time from start of treatment(SoT)/randomization up to event or to date of last contact(pts without event).Definition event: non-response,progressive disease or relapse,treatment related death,death of any other cause or diagnosis of secondary malignancies. 2.Immune reconstitution rate: percentage of pts achieving age adjusted normal B-cell counts(CD19+ subpopulations,normal age adjusted range) 12 months after SoT.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 13
SCP142361 · ATC
- Active substance
- Cytarabine
- Substance synonyms
- ARA-C, CYTOSINE ARABINOSIDE
- Route of administration
- INTRAVENOUS
- Max daily dose
- 6000 mg/m2 milligram(s)/square meter
- Max total dose
- 25200 mg/m2 milligram(s)/square meter
- Max treatment duration
- 8 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP142361 · ATC
- Active substance
- Cytarabine
- Substance synonyms
- ARA-C, CYTOSINE ARABINOSIDE
- Route of administration
- INTRATHECAL USE
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 450 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BC01 — CYTARABINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP4338931 · ATC
- Active substance
- Vinblastine Sulfate
- Substance synonyms
- VINBLASTINE SULPHATE
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 8 mg milligram(s)
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01CA02 — VINCRISTINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1712543 · ATC
- Active substance
- Doxorubicin
- Substance synonyms
- ADRIAMYCIN
- Route of administration
- INTRAVENOUS
- Max daily dose
- 25 mg/m2 milligram(s)/square meter
- Max total dose
- 100 mg/m2 milligram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01DB01 — DOXORUBICIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP10332310 · ATC
- Active substance
- Dexamethasone Acetate
- Route of administration
- INTRAVENOUS
- Max daily dose
- 20 mg/m2 milligram(s)/square meter
- Max total dose
- 480 mg/m2 milligram(s)/square meter
- Max treatment duration
- 39 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB02 — DEXAMETHASONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP24437829 · ATC
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Route of administration
- INTRAVENOUS
- Max daily dose
- 375 mg/m2 milligram(s)/square meter
- Max total dose
- 2625 mg/m2 milligram(s)/square meter
- Max treatment duration
- 7 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01XC02 — RITUXIMAB
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP15687495 · ATC
- Active substance
- Abiraterone Acetate
- Route of administration
- INTRATHECAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 150 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- Authorisation status
- Authorised
- ATC code
- H02AB06 — PREDNISOLONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP2702116 · ATC
- Active substance
- Vindesine Sulfate
- Substance synonyms
- VINDESINE SULPHATE
- Route of administration
- INTRAVENOUS
- Max daily dose
- 5 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01CA03 — VINDESINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP6155697 · ATC
- Active substance
- Etoposide
- Route of administration
- INTRAVENOUS
- Max daily dose
- 200 mg/m2 milligram(s)/square meter
- Max total dose
- 1400 mg/m2 milligram(s)/square meter
- Max treatment duration
- 10 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01CB01 — ETOPOSIDE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1036484 · ATC
- Active substance
- Methotrexate
- Route of administration
- INTRATHECAL
- Max daily dose
- 12 mg milligram(s)
- Max total dose
- 180 mg milligram(s)
- Max treatment duration
- 15 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BA01 — METHOTREXATE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1036484 · ATC
- Active substance
- Methotrexate
- Route of administration
- INTRAVENOUS
- Max daily dose
- 8 gm/m2 gram(s)/square meter
- Max total dose
- 23 gm/m2 gram(s)/square meter
- Max treatment duration
- 4 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BA01 — METHOTREXATE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
—
SCP1728208 · ATC
- Route of administration
- INTRAVENOUS
- Max daily dose
- 400 mg/m2 milligram(s)/square meter
- Max total dose
- 2400 mg/m2 milligram(s)/square meter
- Max treatment duration
- 8 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AA01 — CYCLOPHOSPHAMIDE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP5478032 · ATC
- Active substance
- Ifosfamide
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1600 mg/m2 milligram(s)/square meter
- Max total dose
- 8000 mg/m2 milligram(s)/square meter
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01AA06 — IFOSFAMIDE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitaetsklinikum Muenster AöR
- Sponsor organisation
- Universitaetsklinikum Muenster AöR
- Address
- Gebaeude D5, Albert-Schweitzer-Campus 1, Sentrup Albert-Schweitzer-Campus 1 Sentrup
- City
- Muenster
- Postcode
- 48149
- Country
- Germany
Scientific contact point
- Organisation
- Universitaetsklinikum Muenster AöR
- Contact name
- NHL-BFM study center
Public contact point
- Organisation
- Universitaetsklinikum Muenster AöR
- Contact name
- NHL-BFM study center
Third parties 4
| Organisation | City, country | Duties |
|---|---|---|
| Universitaet Muenster ORG-100008258
|
Muenster, Germany | Code 10 |
| Medizinische Hochschule Hannover ORG-100024473
|
Hanover, Germany | Data management, E-data capture |
| Universitaet Muenster ORG-100008258
|
Muenster, Germany | On site monitoring, Code 12, Code 8 |
| Odense University Hospital ORG-100007716
|
Odense C, Denmark | On site monitoring |
Locations
7 EU/EEA countries · 78 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruitment ended | 40 | 5 |
| Czechia | Ongoing, recruitment ended | 40 | 1 |
| Denmark | Ongoing, recruitment ended | 35 | 4 |
| Finland | Ongoing, recruitment ended | 35 | 5 |
| Germany | Ongoing, recruitment ended | 375 | 53 |
| Norway | Ongoing, recruitment ended | 30 | 4 |
| Sweden | Ongoing, recruitment ended | 50 | 6 |
| Rest of world
Switzerland
|
— | 45 | — |
Investigational sites
Kepler Universitaetsklinikum GmbH
MC IV., Päd. Onkologie, Krankenhausstrasse 26-30, 4020, Linz
St. Anna Kinderspital GmbH
Pediatric Hematology and Oncology, Kinderspitalgasse 6, Alsergrund, Vienna
Medizinische Universitaet Innsbruck
Pädiatrie I, Department für Kinder- und Jugendheilkunde, Anichstrasse 35, 6020, Innsbruck
Medical University Of Graz
Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, Neue Stiftingtalstrasse 6, 8010, Graz
Gemeinnutzige Salzburger Landes kliniken Betriebsgesellschaft mbH
UK für Kinder- und Jugendheilkunde der PMU Salzburg, Landeskrankenhaus, Muellner Hauptstrasse 48, 5020, Salzburg
Fakultni Nemocnice V Motole
Klinika detske hematologie a onkologie, V Uvalu 84, 150 06, Prague 5
Aarhus Universitetshospital
Department of Paediatric and Adolescent Medicine, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Rigshospitalet
Department of Pediatrics and Adolescent Medicine, Blegdamsvej 9, 2100, Copenhagen Oe
Odense University Hospital
H. C. Andersens Children's Hospital, J B Winsloews Vej 4, 5000, Odense C
Aalborg University Hospital
The Children and Youth Department, Reberbansgade 15, 9000, Aalborg
Turku University Hospital
Lasten ja nuorten klinikka, Savitehtaankatu 1, 20520, Turku
Oulu University Hospital
Lasten ja nuorten tulosalue, Kajaanintie 50, 90220, Oulu
Kuopio University Hospital
Lasten ja nuorten klinikka, Puijonlaaksontie 2, P. O. Box 1777, Kuopio
Tampere University Hospital
Lasten ja nuorten klinikka, Teiskontie 35, 33520, Tampere
HUS Helsinki University Hospital
HUS Uusi Lastensairaala, Haartmaninkatu 4, 00290, Helsinki
Universitaetsmedizin Goettingen
Universitäts-Kinderklinik, Pädiatrie I, Robert-Koch-Strasse 40, Weende, Goettingen
Rostock University Medical Center
Kinder- und Jugendklinik Päd. Hämatologie und Onkologie Ernst-Heydemannstr. 8, Schillingallee 35, Hansaviertel, Rostock
Gemeinschaftskrankenhaus Herdecke gGmbH
Kinder- und Jugendmedizin Päd. Hämatologie / Onkologie, Gerhard-Kienle-Weg 4, Westende, Herdecke
University Hospital Jena KöR
Klinik für Kinder- und Jugendmedizin, Am Klinikum 1, Lobeda, Jena
Vestische Kinder- und Jugendklinik Datteln
Kinder- und Jugendklinik, Dr.-Friedrich-Steiner-Str. 5, 45711, Datteln
Klinikum Der Landeshauptstadt Stuttgart gKAöR
Zentrum für Kinder- und Jugendmedizin Pädiatrie 5 (Onkologie, Hämatologie, Immunologie), Kriegsbergstrasse 62, Mitte, Stuttgart
Universitaetsklinikum Essen AöR
Zentrum für Kinder- und Jugendmedizin Hämatologie / Onkologie, Hufelandstrasse 55, Holsterhausen, Essen
Westfaelische Wilhelms-Universitaet Muenster
Klinik für Kinder- und Jugendmedizin Abt. Pädiatrische Hämatologie und Onkologie, Gebaeude A1, Albert-Schweitzer-Campus 1, Muenster
Carl Thiem Klinikum gGmbH
Kinderklinik Station 5e, Thiemstrasse 111, Spremberger Vorstadt, Cottbus
Asklepios Klinik Sankt Augustin GmbH
Kinder- und Jugendmedizin Kinder-Hämatologie und Onkologie, Arnold-Janssen-Strasse 29, 53757, Sankt Augustin
Cnopf'sche Kinderklinik
Kliniken Hallerwiese / Cnopf'sche Kinderklinik Pädiatrische Hämatologie /Onkologie, St.-Johannis-Mühlgasse 19, 90419, Nuernberg
University Medicine Greifswald
Klinik und Poliklinik für Kinder- und Jugendmedizin Abt. Pädiatrische Onkologie und Hämatologie, Ferdinand Sauerbruch Strasse, 17475, Greifswald
Klinikum rechts der Isar der TU Muenchen AöR
Klinikum Schwabing Kinderklinik der TU Päd. Hämatologie / Onkologie Station 24d Kölner Platz 1, Ismaninger Strasse 22, Au-Haidhausen, Munich
University Medical Centre Schleswig-Holstein
Campus Lübeck Klinik für Kinder- und Jugendmedizin Hämatologie und Onkologie, Ratzeburger Allee 160, 23538, Lübeck
Medical Center - University Of Freiburg
Zentrum für Kinder- und Jugendmedizin Klinik IV: Päd. Hämatologie und Onkologie, Mathildenstrasse 1, Stuehlinger, Freiburg Im Breisgau
Helios Kliniken Schwerin GmbH
Klinik für Kinder- und Jugendmedizin Station A1, Wismarsche Strasse 393-397, 19049, Schwerin
Universitaetsklinikum Bonn AöR
Abt. Päd. Hämatologie / Onkologie Adenaueralle 119, Venusberg-Campus 1, Venusberg, Bonn
Universitaetsklinikum Aachen AöR
Klinik für Kinder - und Jugendmedizin Hämatologie / Onkologie, Pauwelsstrasse 30, 52074, Aachen
Saarland University Hospital
Päd. Hämatologie und Onkologie, Geb. 9, Gebaeude 9, Kirrberger Strasse 100, Homburg
Technische Universitat Dresden
Klinik für Kinder- und Jugendmedizin, Fetscherstrasse 74, Johannstadt-Nord, Dresden
Universitaetsklinikum Erlangen AöR
Klinik für Kinder- und Jugendmedizin Pädiatrische Onkologie / Hämatologie, Loschgestrasse 15, Innenstadt, Erlangen
Muhlenkreiskliniken AöR
Klinik für Kinder- und Jugendmedizin Päd. Hämatologie / Onkologie Station E 22, Hans-Nolte-Strasse 1, Haeverstaedt, Minden
Staedtisches Klinikum Braunschweig gGmbH
Zentrum für Kinder- und Jugendmedizin, Salzdahlumer Straße 90, Freisestrasse 9-10, 38118, Brunswick
Goethe University Frankfurt
Klinik für Kinder- und Jugendmedizin Pädiatrische Hämatologie und Onkologie, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Universitaetsklinikum Mannheim GmbH
Universitäts-Kinderklinik Päd. Onkologie /Hämatologie, Theodor-Kutzer-Ufer 1-3, Wohlgelegen, Mannheim
Staedtisches Klinikum Karlsruhe gGmbH
Kinderklinik Station S 24, Moltkestrasse 90, Weststadt, Karlsruhe
Universitaetsklinikum Ulm AöR
Klinik für Kinder- und Jugendmedizin Päd. Hämatologie und Onkologie, Eythstrasse 24, Mitte, Ulm
Klinikum Oldenburg AöR
Zentrum für Kinder- und Jugendmedizin Abt. Hämatologie / Onkologie, Rahel-Straus-Strasse 10, Kreyenbrueck, Oldenburg
Universitaetsklinikum Tuebingen AöR
Klinik für Kinderheilkunde und Jugendmedizin Päd. Hämatologie / Onkologie, Hoppe-Seyler-Strasse 1, Nordstadt, Tuebingen
Klinikum der Universitaet Muenchen AöR
Dr. von Haunersches Kinderspital Pädiatrische Hämatologie / Onkologie, Lindwurmstrasse 4, Ludwigsvorstadt-Isarvorstadt, Munich
Klinikum Dortmund gGmbH
Klinik für Kinder- und Jugendmedizin Station K1, Abt. Päd. Onkologie / Hämatologie, Beurhausstrasse 40, Mitte, Dortmund
Universitaetsklinikum Duesseldorf AöR
Zentrum für Kinder- und Jugendmedizin Klinik für Päd. Hämatologie und Onkologie, Moorenstrasse 5, Bilk, Duesseldorf
Medizinische Hochschule Hannover
Kinderheilkunde Päd. Hämatologie / Onkologie, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Gemeinschaftsklinikum Mittelrhein gGmbH
Klinik für Kinder- und Jugendmedizin Pädiatrische Hämatologie und Onkologie, Koblenzer Str 115-155, 56073, Koblenz
Evangelisches Klinikum Bethel gGmbH
Klinik für Kinder- und Jugendmedizin Bethel/ Kinderzentrum Hämatologie / Onkologie, Grenzweg 10, Kantensiek 11, Gadderbaum, Bielefeld
Universitaetsklinikum Augsburg
Schwäbisches Kinderkrebszentrum I. Klinik für Kinder und Jugendliche Hämatologie / Onkologie, Stenglinstrasse 2, Kriegshaber, Augsburg
Helios Klinikum Berlin-Buch GmbH
Kinderklinik Pädiatrische Hämatologie und Onkologie, Schwanebecker Chaussee 50, Buch, Berlin
University Medical Center Hamburg-Eppendorf
Zentrum für Kinder- und Jugendmedizin Abt. Pädiatrische Hämatologie und Onkologie, Martinistrasse 52, Eppendorf, Hamburg
Universitaetsklinikum Heidelberg AöR
Abt. Hämatologie / Onkologie, Im Neuenheimer Feld 430, Neuenheim, Heidelberg
University Medical Centre Schleswig-Holstein
Campus Kiel Klinik für Allgemeine Pädiatrie Päd. Onkologie / Hämatologie, Arnold-Heller-Strasse 3, Brunswik, Kiel
Klinikum Kassel GmbH
Gesundheit Nordhessen, Holding AG Klinik für pädiatrische Hämatologie und Onkologie, Moenchebergstrasse 41-43, Fasanenhof, Kassel
University Hospital Cologne AöR
Klinik für Kinder- und Jugendmedizin Abt. Kinderonkologie und -hämatologie, Kerpener Strasse 62, Lindenthal, Cologne
Universitaetsmedizin Der Johannes Gutenberg-Universitaet Mainz
Zentrum für Kinder- und Jugendmedizin Pädiatrische Hämatologie / Onkologie, Langenbeckstrasse 1, Oberstadt, Mainz
Helios Klinikum Erfurt GmbH
Klinik für Kinder- und Jugendmedizin Päd. Onkologie / Hämatologie, Nordhaeuser Strasse 74, Andreasvorstadt, Erfurt
Martin-Luther-Universitaet Halle-Wittenberg
Klinik für Kinder- und Jugendmedizin Pädiatrische Hämatologie / Onkologie, Ernst-Grube-Strasse 40, Kroellwitz, Halle (Saale)
Justus-Liebig-Universitaet Giessen
Zentrum für Kinderhämatologie und -onkologie, Feulgenstrasse 10-12, 35392, Giessen
Charite Universitaetsmedizin Berlin KöR
Zentrum für Kinder- und Jugendmedizin Abt. Hämatologie / Onkologie, Augustenburger Platz 1, Wedding, Berlin
Klinikum Bremen-Mitte gGmbH
Eltern-Kind-Zentrum Prof. Hess Kinderonkologisches Zentrum-Station 3, Strasse-Juergen-Strasse 1, Hulsberg, Bremen
Universitaetsklinikum Regensburg
Klinik für Kinder- und Jugendmedizin Abt. Päd. Hämatologie, Onkologie, SZT, Franz-Josef-Strauss-Allee 11, Grass-Oberisling, Regensburg
Universitaet Leipzig
Depart. für Frauen-/Kindermedizin Selbständige Abteilung für Onkologie, Hämatologie/Hämostaselogie, Liebigstrasse 22, Zentrum-Suedost, Leipzig
Universitaetsklinikum Wuerzburg AöR
Päd. Onkologie und Hämatologie, Josef-Schneider-Strasse 2, Grombuehl, Wuerzburg
Helios Klinikum Krefeld GmbH
Zentrum für Kinder- und Jugendmedizin Päd. Hämatologie/Onkologie, Lutherplatz 40, Diessem/lehmheide, Krefeld
Universitaetsklinikum Magdeburg AöR
Kinderklinik Päd. Hämatologie / Onkologie, Leipziger Strasse 44, 39120, Magdeburg
University Hospital Of North Norway HF
Pediatric, Sykehusvegen 38, 9019, Tromsoe
Helse Bergen HF
Pediatric, Jonas Lies Vei 65, 5021, Bergen
St. Olavs Hospital HF
Pediatric, Ragnhilds Gate 15, 7030, Trondheim
Oslo University Hospital HF
Pediatric, Taarnbygget, Kirkeveien 166, Oslo
Region Vaesterbotten
Pediatric Oncology, Koksvagen 11, Alidhem, Umea
Uppsala University Hospital
Pediatric Oncology, Akademiska Sjukhuset, 751 85, Uppsala
Karolinska University Hospital
Pediatric Oncology, Eugeniavagen 3, 171 64, Solna
Region Skane Skanes Universitetssjukhus
Pediatric Oncology, Entregatan 7, Lunds Allhelgonafors, Lund
Linkoping University Hospital Region Ostergotland
Pediatric Oncology, Universitetssjukhuset I Linkoping, 581 85, Linkoping
Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vastra Gotalandsregionen
Pediatric Oncology, Behandlingsvagen 7, Harlanda, Gothenburg
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Austria | 2018-04-11 | 2018-04-22 | 2025-03-07 | ||
| Czechia | 2018-08-31 | 2018-11-14 | 2025-03-07 | ||
| Denmark | 2019-04-23 | 2019-09-02 | 2025-03-07 | ||
| Finland | 2018-01-03 | 2018-06-26 | 2025-03-07 | ||
| Germany | 2017-07-12 | 2017-08-21 | 2025-03-07 | ||
| Norway | 2018-01-10 | 2018-03-07 | 2025-03-07 | ||
| Sweden | 2017-07-12 | 2017-11-10 | 2025-03-07 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 68 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-505509-18_redacted | 3.1 |
| Protocol (for publication) | D4_Patient facing documents Follow-up Plan_DE_redacted | 3.0 |
| Recruitment arrangements (for publication) | K1 Recruitment arrangements FI | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangement Austria | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement Sweden | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements CZ | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements Denmark | 1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements Norway | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment_Arrangement_Germany | 1 |
| Subject information and informed consent form (for publication) | BNHL2013_ICF_CZ_ parents | 3.0 |
| Subject information and informed consent form (for publication) | BNHL2013_ICF_CZ_12-14 yr | 3.0 |
| Subject information and informed consent form (for publication) | BNHL2013_ICF_CZ_15-17 yr | 3.0 |
| Subject information and informed consent form (for publication) | BNHL2013_ICF_CZ_18 yr | 3.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_15_17 yr_ R3_ R4 | 3.1 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_15_17 yr_R1_R2 | 3.1 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_15_17 yr_R2 st III | 2.2 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_18yr_R1_ R2 | 3.1 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_18yr_R2 st III | 2.2 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_18yr_R3_R4 | 3.1 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_Parents R1_R2 | 3.1 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_Parents R2 st III | 2.2 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Denmark_Parents R3_R4 | 3.1 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Finland_Age_Range_10 14yrs_redacted | 9.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Finland_Age_Range_15 17yrs_redacted | 11.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Finland_Age_Range_6 9yrs_redacted | 8.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Finland_Age_Range_parents of 0 14 yrs old participant_redacted | 11.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Finland_Age_Range_parents of 15 17 yrs old participant_redacted | 7.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Germany_Parents_R1R2_redacted | 3.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SIS and ICF_Germany_Parents_R3R4_redacted | 3.0 |
| Subject information and informed consent form (for publication) | BNHL2013_SISandICF_Norway_Age_below 12 y | 2.1 |
| Subject information and informed consent form (for publication) | BNHL2013_SISandICF_Norway_Parents | 2.4 |
| Subject information and informed consent form (for publication) | BNHL2013_SISandICF_Sweden_Age_parents_redacted | 3.2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Sweden age12-14y_redacted | 3.2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Sweden age15-17y_redacted | 3.2 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Sweden age6-11y_redacted | 3.2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany 16-17yr_R1R2_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany 16-17yr_R3R4_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany children 12-15yr_R1R2_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany children 12-15yr_R3R4_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany children 8-11yr | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany children under 8yr | 3.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany re-consent legal competence_R1R2_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany re-consent legal competence_R2III_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Germany re-consent legal competence_R3R4_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Norway 12-18yr | 2.3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF supplement parents Germany_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Austria_adolescents_redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Austria_children | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Austria_children younger | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Austria_contacts_redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Austria_parents_redacted | 6.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Austria_re-consent legal competence_redacted | 6.1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPc_Cyclophosphamide Inj 500 mg_Baxter | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPc_Cytarabine 20mg-ml_Pfizer | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC_Dexamethasone 3_8mg-ml_Aspen | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC_Doxorubicin Sol Inj_Pfizer | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPc_Eldisine Powder Sol Inj 5mg_Genus | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC_Etoposide inf 20mg-ml_medac | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPc_Ifosfamide Inj 1g_Baxter | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPc_Methotrexate 25mg-ml | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPC_Rituximab_MabThera_ 100mg_Roche | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPc_Solu-Decortin | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | SmPc_Vincristine Sulphate_Hospira | 2 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-505509-18 | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-505509-18_AT | 3.1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-505509-18_NO | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2023-505509-18_SE | 3.0 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis_2023-505509-18_ CZ_redacted | 3.0 |
Application history
8 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-08-03 | Germany | Acceptable 2023-09-20
|
2023-09-21 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-10-02 | Germany | Acceptable 2024-11-14
|
2024-11-15 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-02-18 | Germany | Acceptable | 2025-03-19 |
| 4 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-02-18 | Acceptable | 2025-04-06 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-03-11 | Acceptable | 2025-03-17 | |
| 6 | SUBSTANTIAL MODIFICATION | SM-6 | 2026-01-26 | Germany | Acceptable | 2026-02-06 |
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-03-11 | Germany | Acceptable | 2026-03-11 |
| 8 | SUBSTANTIAL MODIFICATION | SM-7 | 2026-04-09 | Germany | Acceptable | 2026-04-15 |