High Risk Neuroblastoma Study 1.8 of SIOP-Europe (SIOPEN)
NCT ID: NCT01704716
Last Updated: 2020-10-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
3300 participants
INTERVENTIONAL
2002-02-28
2026-09-30
Brief Summary
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The protocol consists of a rapid, dose intensive induction chemotherapy, peripheral blood stem cell harvest, attempted complete excision of the primary tumour, myeloablative therapy followed by peripheral blood stem cell rescue, radiotherapy to the site of the primary tumour and immunotherapy (R4 randomization - isotretinoin and ch14.18/CHO (Dinutuximab beta, Qarziba ®).), with or without s.c. aldesleukin (IL-2)). Patients diagnosed after the closure of R3 randomization will not be R4 randomized. For these patients the use of ch14.18/CHO antibody is recommended without scIL-2 as continuous infusion as standard of care outside of controlled trials. ch14.18/CHO received marketing authorization by EMA in May 2017 (Qarziba ®).
In the induction phase, all patients receive Rapid COJEC following the result of the R3 randomization which was closed on June 8th, 2017 after inclusion of 630 patients as planned.
Following induction treatment peripheral blood stem cell harvest (PBSCH) is performed and complete excision of the primary tumour will be attempted.
Patients with an inadequate metastatic response to allow BuMel MAT followed by PBSCR at the end of induction should receive 2 TVD (Topotecan, Vincristine, Doxorubicin) cycles.
After Rapid COJEC induction, localized patients will proceed to consolidation. Patients aged 12-18 months at diagnosis, with stage 4 neuroblastoma, no MYCN amplification and without segmental chromosomal alterations (SCAs) are thought to have a good prognosis and will stop treatment after induction therapy and surgery to the primary tumour.
Consolidation consists of BuMel MAT based on the results of the R1 randomization followed by peripheral blood stem cell rescue (PBSCR) and radiotherapy to the site of the primary tumour.
The R2 immunotherapy randomization using ch14.18/CHO as 8 hour infusion on 5 consecutive days ( total dose (100mg/m²) with or without aldesleukin (IL-2) alternated with isotretinoin (13-cis-RA) is closed.
The amended R4 immunotherapy randomization using ch14.18/CHO as continuous infusion (total dose 100mg/m² over 10 days) with or without aldesleukin (IL-2) alternated with isotretinoin (13-cis-RA) has accrued according to plan with results pending awaiting data maturity and DMC approval.
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Detailed Description
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* disseminated disease (INSS stage 4: about 40 to 50% of all neuroblastoma) over the age of one or
* INSS stage 2 and 3 disease with amplification of the MycN proto-oncogene Between 10% and 20% of children with stage 3 and occasional patients with stage 2 disease are characterized by amplification of the MycN gene in their tumours. This biological characteristic has clearly been shown to be associated with a greater risk of relapse and death from disease progression. These patients may benefit from very aggressive treatment and, based on this hypothesis, they are included in this protocol. Infants (\< 12 months at diagnosis) with MYCN amplified tumors are included.
Children with this type of presentation and age represent the largest neuroblastoma subgroup. Their prognosis remains poor in most cases and our ability to predict the clinical course and the outcome of the individual patient is modest.
Primary objectives:
R0 randomization: R0 was opened with the study activation in February 2002 and closed in November 2005. The randomized use of G-CSF during COJEC induction resulted in the recommendation of the prophylactic use of G-CSF to prevent episodes of febrile neutropenia (Ladenstein R, Valteau-Couanet D, Brock P, et al. Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study. J Clin Oncol. 2010 Jul 20;3516-24).
R1 randomization: R1 was opened with the study activation in February 2002 and closed in 10/2010 following the results showing significant superiority of myeloablative therapy (MAT) with busulfan and melphalan over continuous infusion of carboplatin, etoposide and melphalan (CEM). BuMel is now the standard MAT (Ladenstein R, Pötschger U, Pearson ADJ, et al. Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomized, multi-arm, open-label, phase 3 trial. Lancet Oncol. 2017 Apr;500-14).
R2 randomization: R2 was activated in November 2006 (13-cis retinoic acid +/- chimeric ch14.18/CHO antibody), modified in July 2009 and suspended in August 2013. R2 randomization tested the hypothesis that immunotherapy with ch14.18/CHO and subcutaneous aldesleukin (IL-2, Proleukin®), following MAT and autologous stem cell transplantation, in addition to differentiation therapy with 13-cis retinoic acid, will improve 3-year EFS in patients with high-risk neuroblastoma (ASCO 2016: Ladenstein R, et al J Clin Oncol 34, 2016 (suppl; abstr 10500)).
R3 randomization: R3 was opened in June 2011 and tests the hypothesis that modified N7 induction regimen will improve the metastatic response rates or event free survival (EFS) as compared to Rapid COJEC. As of June 8th, 2017 R3 randomization reached the target of 630 randomized patients as planned. There was no difference in event free survival rate between both regimens (Rapid COJEC and modified N7), but modified N7 had a significantly higher grade 3 and 4 toxicity profile. Therefore, Rapid COJEC is maintained as the SIOPEN standard induction treatment with G-CSF support based on the results of the R0 randomization open from 2002 top 2005 This change has been implemented in amendment 8 of the protocol.
R4 randomization: R4 was activated in April 2014. The SIOPEN long term infusion (LTI) ch14.18/CHO trial successfully lowered the toxicity profile by prolonging the infusion time of the same total ch14.18/CHO antibody dose of 100 mg/m² to 10 days of continuous infusion in relapsed /refractory patients. Hence the HRNBL1/SIOPEN study committee wished to implement this more favorable immunotherapy dosing schedule for the time till the induction question R3 was answered and the HRNBL1/SIOPEN trial may be closed. Considering the high R2 dropout rate of patients unable to receive all immunotherapy cycles in the IL-2 s.c. combination treatment arm and not observing this effect in the current SIOPEN LTI trial, it is suggested to address the IL-2sc dose in the new R4. Therefore the potential synergistic effect of sc IL-2 will be addressed again with 50% of the original s.c. IL-2 dose. The IL-2sc dose will hence be reduced to 3 x 106 IU IL-2/m2/day s.c. in the HR-NBL1/SIOPEN R4 amendment instead of 6 x 106 IU IL-2/m2/day s.c as used in the SIOPEN LTI trial. In the second week of each IT course s.c.IL-2 will be given on days 2, 4, 6, 8, 10 in parallel to the ch14.18/CHO ctn infusion and not during the first 5 days in week 2 as scheduled in the SIOPEN LTI trial. R4 randomization is closed for patients diagnosed after June 8th, 2017, the closure date of R3 randomization. For these patients the use of ch14.18/CHO antibody is recommended without scIL-2 as continuous infusion (total dose 100 mg/m² over 10 days) as standard of care outside of controlled trials without scIL-2. The ch14.18/CHO monoclonal antibody received marketing authorization by EMA in May 2017 (dinutuximab beta, Qarziba®).
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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R0: COJEC plus G-CSF
Patients randomised to G-CSF during induction treatment (Rapid COJEC) received a single daily subcutaneous injection of 5 microgram/kg/day G-CSF (filgrastim) beginning 24 hours after the last chemotherapy dose.
Carboplatin
Carboplatin is given during induction Treatment (R3 randomisation: Rapid COJEC arm)
Etoposide
Etoposide is given during Induction Treatment (both R3 randomisation arms)
Cisplatin
Cisplatin is given during Induction Treatment (both R3 randomisation arms)
Cyclophosphamide
Cyclophosphamid is given during Induction Treatment (both R3 randomisation arms)
G-CSF
G-CSF is given during Induction Treatment
R0: COJEC
Induction treatment (COJEC) without filgrastim Patients randomised to Rapid COJEC alone will receive induction Treatment without G-CSF
Vincristine
given during Rapid COJEC and modified N7 therapy
Carboplatin
Carboplatin is given during induction Treatment (R3 randomisation: Rapid COJEC arm)
Etoposide
Etoposide is given during Induction Treatment (both R3 randomisation arms)
Cisplatin
Cisplatin is given during Induction Treatment (both R3 randomisation arms)
Cyclophosphamide
Cyclophosphamid is given during Induction Treatment (both R3 randomisation arms)
R1: BuMel MAT
The BuMel MAT regimen consists of oral administration of busulphan and the short i.v. infusion of melphalan.
In July 2007 (amendment 3) oral busulfan was changed to i.v. Busulfan (Busilvex)
Busulfan
In case i.v. busulfan is not available, the use of oral busulfan is permitted, although not recommended.
Melphalan
Melphalan is given during MAT treatment
R1: CEM MAT
The CEM MAT regimen uses three drugs: the dose of Carboplatin must be based on renal function with a target area under the concentration versus time curve (AUC) of 16.4 mg/ml.min, etoposide 350 mg/m2/course and melphalan 210 mg/m2/course
Carboplatin
Carboplatin is given during induction Treatment (R3 randomisation: Rapid COJEC arm)
Etoposide
Etoposide is given during Induction Treatment (both R3 randomisation arms)
Melphalan
Melphalan is given during MAT treatment
R2: ch14.18/CHO
ch14.18/CHO is given at a dose of 20 mg/m2/day over five days every four weeks for five courses
ch14.18/CHO
ch14.18/CHO antibody is given during MRD treatment
R2: ch14.18/CHO plus Aldesleukin
Patients randomised to receive ch14.18/CHO plus Aldesleukin
Aldesleukin
Aldesleukin is given during MRD Treatment for patients randomised to the arm with IL-2
ch14.18/CHO
ch14.18/CHO antibody is given during MRD treatment
R3: COJEC Induction
Rapid COJEC induction treatment is applied over ten weeks; three different courses are given every ten days:
Course A (given on days 0 and 40): vincristine, carboplatin, and etoposide Course B (given on days 10, 30, 50, and 70): vincristine and cisplatin Course C (given on days 20 and 60): vincristine, etoposide, and cyclophosphamide
Vincristine
given during Rapid COJEC and modified N7 therapy
Carboplatin
Carboplatin is given during induction Treatment (R3 randomisation: Rapid COJEC arm)
Etoposide
Etoposide is given during Induction Treatment (both R3 randomisation arms)
Cisplatin
Cisplatin is given during Induction Treatment (both R3 randomisation arms)
Cyclophosphamide
Cyclophosphamid is given during Induction Treatment (both R3 randomisation arms)
R3: Modified N7
The modified N7 induction is a dose intense induction chemotherapy regimen including two putatively non cross-resistent drug combinations: high-dose cyclophosphamide plus doxorubicin/vincristine (CAV) and high-dose cisplatin/etoposide (P/E).
Vincristine
given during Rapid COJEC and modified N7 therapy
Etoposide
Etoposide is given during Induction Treatment (both R3 randomisation arms)
Cisplatin
Cisplatin is given during Induction Treatment (both R3 randomisation arms)
Cyclophosphamide
Cyclophosphamid is given during Induction Treatment (both R3 randomisation arms)
Doxorubicin
Doxorubicin is given during Induction Treatment (R3 arm modified N7)
R4: cnt inf ch14.18/CHO
ch14.18/CHO is given as continuous Infusion over 10 days at a cumulative dose of 100mg/m2. Patients receive 5 cycles of ch14.18/CHO
ch14.18/CHO
ch14.18/CHO antibody is given during MRD treatment
R4: cnt inf ch14.18/CHO plus Aldesleukin
ch14.18/CHO is given as continuous Infusion over 10 days at a cumulative dose of 100mg/m2. Patients receive 5 cycles of ch14.18/CHO.
In addition, Aldesleukin is given at a dose of 3 x 10e6 on days 1 to 5 and on days 9, 11, 13, 15, and 17 during ch14.18/CHO infusion
Aldesleukin
Aldesleukin is given during MRD Treatment for patients randomised to the arm with IL-2
ch14.18/CHO
ch14.18/CHO antibody is given during MRD treatment
Interventions
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Vincristine
given during Rapid COJEC and modified N7 therapy
Aldesleukin
Aldesleukin is given during MRD Treatment for patients randomised to the arm with IL-2
ch14.18/CHO
ch14.18/CHO antibody is given during MRD treatment
Carboplatin
Carboplatin is given during induction Treatment (R3 randomisation: Rapid COJEC arm)
Etoposide
Etoposide is given during Induction Treatment (both R3 randomisation arms)
Cisplatin
Cisplatin is given during Induction Treatment (both R3 randomisation arms)
Cyclophosphamide
Cyclophosphamid is given during Induction Treatment (both R3 randomisation arms)
Doxorubicin
Doxorubicin is given during Induction Treatment (R3 arm modified N7)
G-CSF
G-CSF is given during Induction Treatment
Busulfan
In case i.v. busulfan is not available, the use of oral busulfan is permitted, although not recommended.
Melphalan
Melphalan is given during MAT treatment
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Age below 21 years.
* High risk neuroblastoma defined as either:
1. INSS stage 2, 3, 4, and 4s with MYCN amplification, or
2. INSS stage 4 without MYCN amplification aged \> 12 months at diagnosis
* Patients who have received no previous chemotherapy except for one cycle of etoposide and carboplatin (VP16/Carbo). In this situation patients will receive Rapid COJEC induction and the first Rapid COJEC cycle may be replaced by the first cycle VP16/Carbo (etoposide / carboplatin).
* Written informed consent, including agreement of parents or legal guardian for minors, to enter a randomised study if the criteria for randomisation are met.
* Tumour cell material available for determination of biological prognostic factors.
* Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
* Registration of all eligibility criteria with the data centre within 6 weeks from diagnosis.
* Provisional follow up of 5 years.
* National and local ethical committee approval.
\-
1 Month
21 Years
ALL
No
Sponsors
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St. Anna Kinderkrebsforschung
OTHER
Responsible Party
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Principal Investigators
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Ruth L Ladenstein, MD, MBA, cPM
Role: PRINCIPAL_INVESTIGATOR
St. Anna Kinderkrebsforschung
Locations
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Ospedale dei Bambini, Palermo
Palermo, , Italy
Ospedale Bambino Gesu
Rome, , Italy
Azienda Ospedaliera Universitaria di Parma-Oncoematologia Pediatrica
Parma, , Italy
Policlinico San Matteo
Pavia, , Italy
Women and Children´s Hospital
Adelaide, , Australia
Lady Cilento Children´s Hospital
Brisbane, , Australia
John Hunter Children's Hospital
Newcastle, , Australia
Royal Children's Hospital Melbourne
Parkville, , Australia
Sydney Children's Hospital
Sydney, , Australia
Children´s Hospital Westmead
Westmead, , Australia
St. Anna Kinderspital
Vienna, Austra, Austria
Univ.-Klinik für Kinder- und Jugendheilkunde Graz
Graz, , Austria
Univ.Klinik f. Kinder-u. Jugendheilkunde Innsbruck
Innsbruck, , Austria
Landes- Kinderklinik Linz
Linz, , Austria
St. Johanns Spital LKH Salzburg
Salzburg, , Austria
Cliniques universitaires St-Luc
Brussels, , Belgium
Hôpital des Enfants
Brussels, , Belgium
University Hospital Gent
Ghent, , Belgium
UZ Gasthuisberg
Leuven, , Belgium
CHR Citadelle
Liège, , Belgium
Clinique de l'Espérance
Montegnée, , Belgium
University Hospital Motol
Prague, , Czechia
Aarhus Universitetshospital
Aarhus, , Denmark
National State Hospital
Copenhagen, , Denmark
University Hospital of Odense
Odense, , Denmark
Skejby Hospital
Skejby, , Denmark
Hopital d'Enfants Dijon
Dijon, , France
CHU de Grenoble
Grenoble, , France
CHR Pellegrin
Le Pellerin, , France
Centre Oscar Lambret de Lille
Lille, , France
Ospedale Civile Spirito Santo
Pescara, , Italy
Ospedale "Infermi "
Rimini, , Italy
Hopitaux de Marseille La Timone
Marseille, , France
CHR de Nantes
Nantes, , France
Hôpital Trousseau Paris
Paris, , France
Institut Curie
Paris, , France
Hôpital American Memorial Hospital
Reims, , France
CHU-Saint Etienne
Saint-Etienne, , France
Hôpital de Hautepierre
Strasbourg, , France
Hôpital D'Enfants de Toulouse
Toulouse, , France
Institut Gustave Roussy
Villejuif, , France
"A&P Kyriakou" Children's Hospital
Athens, , Greece
Aghia Sophia Children's Hospital
Athens, , Greece
MITERA Hospital
Heraklion, , Greece
PEPAGNH University Hospital
Heraklion, , Greece
Madarász Children Hospital Budapest
Budapest, , Hungary
Semmelweis University of Budapest
Budapest, , Hungary
University of Debrecen
Debrecen, , Hungary
University of Pecs
Pécs, , Hungary
University of Szeged
Szeged, , Hungary
Dublin: OLHSC
Dublin, , Ireland
Rambam Medical Centre
Haifa, , Israel
Schneider Children's Medical Center of Israel
Petah Tikva, , Israel
Sheba Medical Center
Tel Aviv, , Israel
Ospedale G. Salesi
Ancona, , Italy
Universitŕ degli studi di Bari
Bari, , Italy
Ospedali Riuniti
Bergamo, , Italy
Ospedale S. Orsola
Bologna, , Italy
Ospedale Regionale per le Microcitemie
Cagliari, , Italy
Azienda Ospedaliera di Cosenza
Cosenza, , Italy
Azienda Ospedaliera A. Meyer
Florence, , Italy
Istituto Giannina Gaslini
Genoa, , Italy
Policlinico Borgo Roma
Roma, , Italy
Istituto Nazionale Tumori di Milano
Milan, , Italy
Azienda Ospedal. Univ. di Modena
Modena, , Italy
Sec. Univ. degli Studi di Napoli - Policlinico
Napoli, , Italy
Clinica di Oncoematologia Pediatrica Padova
Padua, , Italy
Casa Sollievo della Sofferenza
San Giovanni Rotondo, , Italy
O.I.R.M. - S. Anna
Torino, , Italy
Istituto per l'Infanzia "Burlo Garofolo"
Trieste, , Italy
Haukeland University Hospital
Bergen, , Norway
Rikshospitalet
Oslo, , Norway
University Hospital of North-Norway
Tromsø, , Norway
Medical University of Bialystok
Bialystok, , Poland
Medical University of Bydgoszcz
Bydgoszcz, , Poland
Childrens' Hospital in Chorzów
Chorzów, , Poland
Medical University in Gdansk
Gdansk, , Poland
Upper Silesian Centre of Child and Mother's Care
Katowice, , Poland
University Children's Hospital
Krakow, , Poland
Children's University Hospital in Lublin
Lublin, , Poland
University of Medical Sciences Poznan
Poznan, , Poland
Institute Mother and Child
Warsaw, , Poland
Wroclaw Medical University
Wroclaw, , Poland
Ipofg-Crl
Lisbon, , Portugal
University Hospital F. D. Roosevelt
Banská Bystrica, , Slovakia
University Children's Hospital Ljubljana
Ljubljana, , Slovenia
H . Materno-Infantil Teresa Herrera
A Coruña, , Spain
H. General de Alicante
Alicante, , Spain
Hospital Vall d'Hebron
Barcelona, , Spain
Hospital de Cruces
Bilbao, , Spain
Complejo Hospitalario de Jaen
Jaén, , Spain
H. Monteprincipe
Madrid, , Spain
Hospital 12 de Octubre
Madrid, , Spain
H Central de Asturias
Oviedo, , Spain
H. C. U. de Salamanca
Salamanca, , Spain
H. de Donostia Ntra. Sra. de Aranzazu
San Sebastián, , Spain
H. General de Galicia
Santiago de Compostela, , Spain
Hospital Virgen del Rocio
Seville, , Spain
Carlos Haya
Valencia, , Spain
Hospital Infantil La Fe
Valencia, , Spain
H Clinico-Universitario
Zaragoza, , Spain
Queen Silvia's Children's Hospital
Göteburg, , Sweden
Childrens Hospital Linkoping
Linköping, , Sweden
University Children's Hospital
Geneva, , Switzerland
CHUV
Lausanne, , Switzerland
Aberdeen: Royal Aberdeen Children's Hospital
Aberdeen, , United Kingdom
Royal Belfast Hospital for Sick Children
Belfast, , United Kingdom
Birmingham Children's Hospital
Birmingham, , United Kingdom
Bristol Royal Hospital for Children
Bristol, , United Kingdom
Addenbrooke's NHS Trust
Cambridge, , United Kingdom
Llandough Hospital
Cardiff, , United Kingdom
Edinburgh Royal Hospital for Sick Children
Edinburgh, , United Kingdom
Glasgow Royal Hospital for Sick Children
Glasgow, , United Kingdom
Leeds: St James's University Hospital
Leeds, , United Kingdom
Leicester Royal Infirmary
Leicester, , United Kingdom
Liverpool: Alder Hey Children's Hospital
Liverpool, , United Kingdom
Great Ormond Street Hospital
London, , United Kingdom
St Bartholomew's Hospital
London, , United Kingdom
UCLH University College London Hospital
London, , United Kingdom
Royal Manchester Children's Hospital
Manchester, , United Kingdom
Newcastle: Royal Victoria Infirmary
Newcastle, , United Kingdom
Nottingham: Queen's Medical Centre
Nottingham, , United Kingdom
Oxford: John Radcliffe Hospital
Oxford, , United Kingdom
Sheffield Children's Hospital
Sheffield, , United Kingdom
Southampton General Hospital
Southhampton, , United Kingdom
Royal Marsden Hospital
Sutton, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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MD
Role: primary
MD
Role: primary
References
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Ladenstein R, Valteau-Couanet D, Brock P, Yaniv I, Castel V, Laureys G, Malis J, Papadakis V, Lacerda A, Ruud E, Kogner P, Garami M, Balwierz W, Schroeder H, Beck-Popovic M, Schreier G, Machin D, Potschger U, Pearson A. Randomized Trial of prophylactic granulocyte colony-stimulating factor during rapid COJEC induction in pediatric patients with high-risk neuroblastoma: the European HR-NBL1/SIOPEN study. J Clin Oncol. 2010 Jul 20;28(21):3516-24. doi: 10.1200/JCO.2009.27.3524. Epub 2010 Jun 21.
Ladenstein R, Potschger U, Pearson ADJ, Brock P, Luksch R, Castel V, Yaniv I, Papadakis V, Laureys G, Malis J, Balwierz W, Ruud E, Kogner P, Schroeder H, de Lacerda AF, Beck-Popovic M, Bician P, Garami M, Trahair T, Canete A, Ambros PF, Holmes K, Gaze M, Schreier G, Garaventa A, Vassal G, Michon J, Valteau-Couanet D; SIOP Europe Neuroblastoma Group (SIOPEN). Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):500-514. doi: 10.1016/S1470-2045(17)30070-0. Epub 2017 Mar 2.
Ladenstein R, Potschger U, Valteau-Couanet D, Luksch R, Castel V, Yaniv I, Laureys G, Brock P, Michon JM, Owens C, Trahair T, Chan GCF, Ruud E, Schroeder H, Beck Popovic M, Schreier G, Loibner H, Ambros P, Holmes K, Castellani MR, Gaze MN, Garaventa A, Pearson ADJ, Lode HN. Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1617-1629. doi: 10.1016/S1470-2045(18)30578-3. Epub 2018 Nov 12.
Morgenstern DA, Potschger U, Moreno L, Papadakis V, Owens C, Ash S, Pasqualini C, Luksch R, Garaventa A, Canete A, Elliot M, Wieczorek A, Laureys G, Kogner P, Malis J, Ruud E, Beck-Popovic M, Schleiermacher G, Valteau-Couanet D, Ladenstein R. Risk stratification of high-risk metastatic neuroblastoma: A report from the HR-NBL-1/SIOPEN study. Pediatr Blood Cancer. 2018 Nov;65(11):e27363. doi: 10.1002/pbc.27363. Epub 2018 Jul 17.
Berbegall AP, Bogen D, Potschger U, Beiske K, Bown N, Combaret V, Defferrari R, Jeison M, Mazzocco K, Varesio L, Vicha A, Ash S, Castel V, Coze C, Ladenstein R, Owens C, Papadakis V, Ruud E, Amann G, Sementa AR, Navarro S, Ambros PF, Noguera R, Ambros IM. Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study. Br J Cancer. 2018 May;118(11):1502-1512. doi: 10.1038/s41416-018-0098-6. Epub 2018 May 14.
Mueller I, Ehlert K, Endres S, Pill L, Siebert N, Kietz S, Brock P, Garaventa A, Valteau-Couanet D, Janzek E, Hosten N, Zinke A, Barthlen W, Varol E, Loibner H, Ladenstein R, Lode HN. Tolerability, response and outcome of high-risk neuroblastoma patients treated with long-term infusion of anti-GD2 antibody ch14.18/CHO. MAbs. 2018 Jan;10(1):55-61. doi: 10.1080/19420862.2017.1402997. Epub 2017 Dec 5.
Ladenstein R, Potschger U, Valteau-Couanet D, Luksch R, Castel V, Ash S, Laureys G, Brock P, Michon JM, Owens C, Trahair T, Chi Fung Chan G, Ruud E, Schroeder H, Beck-Popovic M, Schreier G, Loibner H, Ambros P, Holmes K, Castellani MR, Gaze MN, Garaventa A, Pearson ADJ, Lode HN. Investigation of the Role of Dinutuximab Beta-Based Immunotherapy in the SIOPEN High-Risk Neuroblastoma 1 Trial (HR-NBL1). Cancers (Basel). 2020 Jan 28;12(2):309. doi: 10.3390/cancers12020309.
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Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
HR-NBL-1.8 / SIOPEN
Identifier Type: -
Identifier Source: org_study_id
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