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High Risk Neuroblastoma Study 1.8 of SIOP-Europe (SIOPEN)
Sponsor: St. Anna Kinderkrebsforschung
Summary
This is a randomized study of the European SIOP Neuroblastoma Group (SIOPEN) in high-risk neuroblastoma (stages 2, 3, 4 and 4s MYCN-amplified neuroblastoma, stage 4 MYCN non amplified \> 12 months at diagnosis). 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.
Official title: High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)
Key Details
Gender
All
Age Range
1 Month - 21 Years
Study Type
INTERVENTIONAL
Enrollment
3300
Start Date
2002-02
Completion Date
2026-09
Last Updated
2020-10-23
Healthy Volunteers
No
Conditions
Interventions
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
Locations (126)
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
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
Istituto Nazionale Tumori di Milano
Milan, Italy
Azienda Ospedal. Univ. di Modena
Modena, Italy
Sec. Univ. degli Studi di Napoli - Policlinico
Naples, Italy
Clinica di Oncoematologia Pediatrica Padova
Padova, Italy
Ospedale dei Bambini, Palermo
Palermo, Italy
Azienda Ospedaliera Universitaria di Parma-Oncoematologia Pediatrica
Parma, Italy
Policlinico San Matteo
Pavia, Italy
Ospedale Civile Spirito Santo
Pescara, Italy
Ospedale "Infermi "
Rimini, Italy
Policlinico Borgo Roma
Roma, Italy
Ospedale Bambino Gesu
Rome, 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