High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN) (HR-NBL2)

February 10, 2023 updated by: Gustave Roussy, Cancer Campus, Grand Paris
This is an international multicenter, open-label, randomized phase III trial including three sequential randomizations to assess efficacy of induction and consolidation chemotherapies and radiotherapy for patients with high-risk neuroblastoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an international multicenter, open-label, randomized phase III trial including three sequential randomizations to assess efficacy of induction and consolidation chemotherapies and radiotherapy for patients with high-risk neuroblastoma.

The first randomization (R-I) will compare the efficacy of two induction chemotherapies (RAPID COJEC and GPOH regimens) in a phase III setting. The primary endpoint will be the 3-year EFS from date of randomization . The R-I randomization will be stratified on age, stage, MYCN status and countries.

The second randomization (R-HDC) will compare the efficacy of single HDC with Bu-Mel versus tandem HDC with Thiotepa followed by Bu-Mel. The primary endpoint is 3-year EFS calculated from the date of the R-HDC randomization. The R-HDC randomization will be stratified on the age, stage, MYCN status, induction chemotherapy regimen, response to induction phase and countries.

The impact of local treatment in this phase III setting will be assessed, according to the presence or not of a macroscopic residual disease after surgery and HDC.

In case of macroscopic residual disease, 21.6 Gy radiotherapy to the preoperative tumor bed will be randomized (R-RTx) versus the same treatment plus a sequential boost of additional 14.4 Gy to the residual tumor. The primary endpoint of R-RTx is 3-year EFS from the date of the R-RTx randomization. The R-RTx randomization will be stratified on age, stage, MYCN status, induction chemotherapy regimen, HDC regimen and countries.

In case of no macroscopic residual disease, 21.6 Gy radiotherapy will be delivered to the preoperative tumor bed.

Study Type

Interventional

Enrollment (Anticipated)

800

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Clayton, Australia, VIC 3168
        • Not yet recruiting
        • Children's Cancer Centre, Monash Children's Hospital
      • Nedlands, Australia, WA, 6009
        • Not yet recruiting
        • Oncology/Haematology Department, Perth Children's Hospital
      • New Lambton Heights, Australia, NSW, 2305
        • Not yet recruiting
        • Children's Cancer & Haematology Services, John Hunter Children's Hospital
      • Sydney, Australia, NSW, 2031
        • Active, not recruiting
        • Australian and New Zealand Children's Hematology/oncology Group
      • Sydney, Australia, NSW, 2031
        • Not yet recruiting
        • sydney children Hospital
      • Westmead, Australia, NSW, 2145,
        • Not yet recruiting
        • Cancer Centre for Children, The Children's Hospital
    • Randwick
      • Sydney, Randwick, Australia, NSW, 2031
        • Not yet recruiting
        • sydney children Hospital
  • Belgium
      • Brussel, Belgium, 1200
        • Not yet recruiting
        • Cliniques Universitaires Saint-Luc (UCL)
      • Brussels, Belgium, 1020
        • Not yet recruiting
        • Hôpital Universitaire des Enfants Reine Fabiola (ULB)
      • Gent, Belgium, 9000
        • Recruiting
        • University Hospital Gent
      • Leuven, Belgium, 3000
        • Not yet recruiting
        • University Hospitals Leuven
      • Liège, Belgium, 4000
        • Not yet recruiting
        • CHR Citadelle
  • Czechia
      • Brno, Czechia, 662 63
        • Not yet recruiting
        • Klinika dětské onkologie FN Brno
    • Prague
      • Prague,, Prague, Czechia, 15006
        • Recruiting
        • University Hospital Motol
  • Denmark
      • Aarhus, Denmark, DK-8200
        • Recruiting
        • Aarhus University Hospital
      • Copenhagen, Denmark, DK-2100
        • Recruiting
        • Department of Paediatrics and Adolescent Medicine, Rigshospitalet
      • Odense, Denmark, DK-5000
        • Not yet recruiting
        • The Hans Christian Andersen Children's Hospital, University of Southern Denmark
  • Finland
      • Helsinki, Finland, 00029
        • Not yet recruiting
        • New Children's Hospital, Helsinki University Hospital, Helsinki and Uusimaa Hospital District
        • Contact:
      • Kuopio, Finland
        • Not yet recruiting
        • Kuopio University Hospital
        • Contact:
      • Oulu, Finland
        • Not yet recruiting
        • Oulu University Hospital
        • Contact:
      • Tampere, Finland
        • Not yet recruiting
        • Tampere University Hospital
        • Contact:
      • Turku, Finland
        • Not yet recruiting
        • Turku University Hospital
        • Contact:
  • France
      • Amiens, France, 80054
        • Recruiting
        • CHU d'Amiens
      • Angers, France
        • Recruiting
        • CHU Angers
      • Besançon, France
        • Recruiting
        • CHU-Pôle Médico-Chirurgical de l'Enfant et l'Adolescant
      • Bordeaux, France, 33600
        • Active, not recruiting
        • CHU Bordeaux
      • Bordeaux, France
        • Recruiting
        • Groupe Hospitalier Pellegrin - Chu - Bordeaux
      • Brest, France, 29609
        • Recruiting
        • CHU Brest
      • Brest, France
        • Recruiting
        • CHU Brest - Hôpital du Morvan
      • Caen, France
        • Recruiting
        • CHU de Caen
      • Caen, France
        • Active, not recruiting
        • Centre Francois Baclesse
      • Clermont-Ferrand, France
        • Recruiting
        • CHU Estaing
      • Dijon, France
        • Active, not recruiting
        • Centre Georges-Francois Leclerc
      • Dijon, France
        • Recruiting
        • Hopital d'enfants Marechal de lattre
      • Grenoble, France
        • Recruiting
        • Hôpital Couple-Enfant CHU de Grenoble
      • La Réunion, France
        • Recruiting
        • Chu de La Reunion - St Denis
      • Lille, France
        • Recruiting
        • Centre Oscar Lambert
      • Limoges, France
        • Recruiting
        • Hôpital de la Mère et de l'Enfant - CHU Limoges
      • Lyon, France
        • Recruiting
        • Centre Leon Berard
      • Marseille, France
        • Recruiting
        • Hôpital La Timone
      • Nancy, France
        • Recruiting
        • CHRU Nancy-Hôpital Brabois Enfant
      • Nancy, France
        • Active, not recruiting
        • Institut de cancérologie de Loraine
      • Nice, France
        • Active, not recruiting
        • Centre Antoine Lacassagne
      • Nice, France
        • Recruiting
        • CHU Nice-Hôpital d'Archet
      • Paris, France
        • Recruiting
        • Hôpital Armand Trousseau
      • Paris, France
        • Recruiting
        • Institut Curie
      • Poitiers, France
        • Recruiting
        • CHU Poitiers
      • Reims, France
        • Recruiting
        • Hôpital Américain -CHU Reims
      • Rennes, France
        • Recruiting
        • CHU Rennes
      • Rennes, France
        • Active, not recruiting
        • Centre Eugène Marquis
      • Rouen, France
        • Recruiting
        • Hôpital des Enfants - CHU Rouen
      • Saint-Herblain, France
        • Active, not recruiting
        • Institut de Cancérologie de l'Ouest - Site René Gauducheau
      • Saint-Étienne, France
        • Recruiting
        • Chu Saint Etienne
      • Strasbourg, France
        • Recruiting
        • CHU Haute Pierre
      • Strasbourg, France
        • Active, not recruiting
        • Institut de Cancerologie Strasbourg
      • Toulouse, France
        • Recruiting
        • Hopital des enfants-CHU Toulouse
      • Toulouse, France
        • Active, not recruiting
        • IUCT Oncopole
      • Tours, France
        • Recruiting
        • Chu Tours Hopital Clocheville
    • Val De Marne
      • Villejuif, Val De Marne, France, 94800
        • Recruiting
        • Gustave Roussy
  • Greece
      • Athens, Greece, 11527
        • Recruiting
        • Children's General Hospital "I AGHIA SOFIA"
      • Athens, Greece, 11527
        • Not yet recruiting
        • Children's General Hospital "P. & A. KYRIAKOU"
      • Athens, Greece
        • Recruiting
        • Children's General Hospital "AGHIA SOFIA"
      • Athens, Greece, 15123
        • Recruiting
        • "MITERA" Private, General, Obstetrics - Gynaecology, Paediatric Clinic S.A.
      • Heraklion, Greece, 71500
        • Recruiting
        • University General Hospital of Heraklion (UnGHH)
      • Thessaloniki, Greece, 54642
        • Recruiting
        • General Hospital of Thessaloniki "Ippokratio"
      • Thessaloniki, Greece, 54621
        • Recruiting
        • University General Hospital of Thessaloniki "Ahepa"
  • Italy
      • Bari, Italy, 70124
        • Recruiting
        • A.O.U Policlinico di Bari
      • Brescia, Italy, 3995041
        • Recruiting
        • Spedali civili Ospedale Dei Bambini Oncoematologia pediatrica e TMO
      • Catania, Italy, 95123
        • Recruiting
        • policlinico rodolico San marco
      • Firenze, Italy, 50139
        • Recruiting
        • Azienda ospedaliero universtaria Anna Meyer
      • Genova, Italy, 16147
        • Recruiting
        • IRCCS "Istituto Giannina Gaslini"
      • Genova, Italy, 16147
        • Recruiting
        • instituto Giannina Gaslini genova
      • Modena, Italy, 41100
      • Parma, Italy, 43126
        • Recruiting
        • Azienda Ospedaliero Universitaria di Parma
      • Pavia, Italy, 27100
        • Recruiting
        • Policlino San matteo di Pavia
      • Rimini, Italy, 47900
        • Not yet recruiting
        • U.O Pediatria, SS Oncoematologia pediatrica
        • Contact:
      • Trieste, Italy, 34137
        • Recruiting
        • IRCCS Burlo Garoflo oncoematologia
      • Verona, Italy, 37126
        • Recruiting
        • U.O.C oncoematologia pediatrica ospedale Donna Bambino
  • Lithuania
      • Vilnius, Lithuania, 08406
        • Not yet recruiting
        • Vilnius University hospital Santaros klinikos
        • Contact:
      • Vilnius, Lithuania, 08660
        • Not yet recruiting
        • National Cancer Institute
        • Contact:
  • Netherlands
      • Groningen, Netherlands, 9700
        • Active, not recruiting
        • Universitair Medisch Centrum Groningen
      • Utrecht, Netherlands, 3584CS
        • Recruiting
        • Princess Maxima Center
  • Norway
      • Haukeland, Norway
        • Not yet recruiting
        • Haukeland University Hospital
      • Oslo, Norway, 0424
        • Recruiting
        • Oslo University Hospital
      • Tromsø, Norway
        • Not yet recruiting
        • University Hospital Northern Norway, Tromsoe
      • Trondheim, Norway
        • Not yet recruiting
        • St Olavs Hospital,
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Recruiting
        • University medical center Ljubljana, University Children's Hospital Ljubljana, Slovenia
  • Spain
      • Balea, Spain, 07010
        • Not yet recruiting
        • Hospital Universitario Son Espases
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Hospital Universitario Vall d´Hebron
      • Cruces, Spain, 48903
        • Not yet recruiting
        • Hospital Universitario Cruces
      • El Palmar, Spain, 30120
        • Not yet recruiting
        • Hospital Clínico Universitario Virgen de la Arrixaca
      • Madrid, Spain, 28046
        • Not yet recruiting
        • Hospital Universitario La Paz
      • Madrid, Spain, 28009
        • Not yet recruiting
        • Hospital Universitario Infantil Niño Jesus
      • Málaga, Spain, 29010
        • Not yet recruiting
        • Hospital Regional Universitario de Malaga
      • San Sebastián, Spain, 20014
        • Not yet recruiting
        • Hospital Universitario Donostia
      • Santiago De Compostela, Spain, 15706
        • Not yet recruiting
        • Hospital Clinico Universitario de Santiago
      • Sevilla, Spain, 41013
        • Not yet recruiting
        • Hospital Universitario Virgen del Rocio
      • Valence, Spain
        • Not yet recruiting
        • Hospital Universitario Politécnico de La FE
  • Sweden
      • Gothenburg, Sweden
      • Linköping, Sweden
        • Not yet recruiting
        • Linköping University Hospital
        • Contact:
          • Lisa Törnudd, MD
      • Lund, Sweden
        • Not yet recruiting
        • Skåne University Hospital
        • Contact:
      • Stockholm, Sweden
      • Umeå, Sweden
      • Uppsala, Sweden
  • Switzerland
      • Aarau, Switzerland, CH-5001
        • Recruiting
        • Kantonsspital Aarau AG Klinik für Kinder und Jugendliche
      • Basel, Switzerland, CH-4031
        • Recruiting
        • Universitäts-Kinderspital beider Basel (UKBB)
      • Bellinzona, Switzerland, CH-6500
        • Recruiting
        • Ospedale San Giovanni Pediatria, Emato-oncologia pediatrica
      • Bern, Switzerland, CH-3010
        • Recruiting
        • Inselspital, Universitätsklinik für Kinderheilkunde
      • Geneva, Switzerland, CH-1205
        • Recruiting
        • HUG Hôpitaux Universitaires de Genève Unité d'Hémato-Oncologie Pédiatrique
      • Lausanne, Switzerland, CH-1011
        • Recruiting
        • CHUV - Centre hospitalier universitaire vaudois
      • Lucerne, Switzerland, CH-6000
        • Recruiting
        • Luzerner Kantonsspital, Kinderspital pädiatrische Hämatologie/Onkologie
      • Saint Gallen, Switzerland, CH-9006
        • Recruiting
        • Ostschweizer Kinderspital Hämatologie/Onkologie Claudiusstrasse 6
      • Zürich, Switzerland, CH-8032
        • Recruiting
        • Division of Pediatric Oncology Universitäts-Kinderspital Zürich
  • United Kingdom
      • Birmingham, United Kingdom, B46NH
        • Recruiting
        • Birmingham Children's Hospital
      • Birmingham, United Kingdom, B46NH
        • Active, not recruiting
        • University Hospitals Birmingham Queen Elisabeth Hospital(UHB)
      • Bristol, United Kingdom, BS1 3NU
        • Recruiting
        • University Hospitals Bristol and Weston NHS Foundation Trust
      • Glasgow, United Kingdom, G34
        • Recruiting
        • Royal Hospital for Children Glasgow
      • Manchester, United Kingdom
        • Recruiting
        • Royal Manchester Children's Hospital
      • Newcastle, United Kingdom
        • Active, not recruiting
        • Royal Victoria Infirmary, Newcastle
      • Sheffield, United Kingdom, S102TH
        • Active, not recruiting
        • Sheffield Children's Hospital
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 20 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

At diagnosis (or up to 21 days after one cycle of chemotherapy for patients with localized neuroblastoma with MYCN amplification).

R-I eligibility criteria:

  1. Established diagnosis of neuroblastoma according to the SIOPEN-modified International Neuroblastoma Risk Group (INRG) criteria, High-risk neuroblastoma defined as:

    • Stage M neuroblastoma above 365 days of age at diagnosis (no upper age limit) and Ms neuroblastoma 12-18 months old, any MYCN status* or
    • L2, M or Ms neuroblastoma any age with MYCN amplification or focal high level MYC or MYCL amplification * In Germany, patients aged less than 18 months with stage M and without MYCN amplification will not be enrolled in HR-NBL2 trial.
  2. No previous chemotherapy or up to 21days one cycle of chemotherapy for patients with localized neuroblastoma with MYCN amplification or patients with metastatic neuroblastoma treated in emergency
  3. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to initiation of treatment. Sexually active patients must agree to use acceptable and appropriate contraception while on HRNBL2 study drug and for one year after stopping the study . Acceptable contraception is defined in CTFG Guidelines "Recommendations related to contraception and pregnancy testing in clinical trials". Female patients who are lactating must agree to stop breast-feeding.
  4. Written informed consent to enter the R-I randomization from patient or parents/legal representative, patient, and age-appropriate assent.
  5. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
  6. Patients should be able and willing to comply with study visits and procedures as per protocol.

In case of parents'/patient's refusal to R-I, or organ toxicity, exclusion criteria at diagnosis, patients can still be enrolled in HR-NBL2 trial with parents'/patient's consent within 3 weeks from the beginning of chemotherapy. Patients will be treated with the standard induction regimen per country (rapid COJEC or GPOH) and will be potentially eligible for subsequent randomizations.

Randomization for HDC strategy will be performed at the end of induction after the disease evaluation and after surgery of the primary tumor for those patients who will receive surgery before HDC.

R-HDC eligibility criteria:

  1. - Stage M neuroblastoma above 365 days of age at diagnosis, any MYCN status, EXCEPT patients with stage M or Ms 12-18 months old with numerical chromosomal alterations only, and in complete metastatic response at the end of induction: in this case, patients will have surgery but will not be eligible for R-HDC and will not be able to pursue the trial.

    OR

    - L2, M or Ms neuroblastoma any age with MYCN amplification or focal high level MYC or MYCL amplification

  2. Age < 21 years

  3. Complete response (CR) or partial response (PR) at metastatic sites:

    • Bone disease: MIBG uptake (or FDG-PET uptake for MIBG-nonavid tumors) completely resolved or SIOPEN score ≤ 3 and at least 50% reduction in mIBG score (or ≤ 3 bone lesions and at least 50% reduction in number of FDG-PET-avid bone lesions for MIBG-nonavid tumors).
    • Bone marrow disease: CR and/or minimal disease (MD) according to International Neuroblastoma Response Criteria [Park JR, JCO 2017; Burchill S, Cancer 2017].
    • Other metastatic sites: complete response after induction chemotherapy +/- surgery.

  4. Acceptable organ function and performance status

    • Performance status ≥ 50%.
    • Hematological status: ANC > 0.5x10^9/L, platelets > 20x 10^9/L
    • Cardiac function (< grade 2)
    • Normal chest X-ray and oxygen saturation.
    • Absence of any toxicity ≥ grade 3.
  5. Sufficient collected stem cells available; minimum required: 6 x 10^6 CD34+ cells/kg body weight stored in 3 separate fractions.
  6. Written informed consent, including agreement of patient or parents/legal guardian for minors, to enter the R-HDC randomization.
  7. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
  8. Patients should be able and willing to comply with study visits and procedures as per protocol.

In case of parents'/patient's refusal, or insufficient stem cells, collection for tandem HDC but with a minimum of 3 x 10^6 CD34+ cells/kg body weight, or in case of patients older than 21 years, or organ toxicity, HDC will consist on the standard HD Bu-Mel and will be eligible for subsequent randomization.

An evaluation of the local disease will be performed after HDC/ASCR and surgery:

  • In case of no local macroscopic disease, all patients will receive 21-Gy radiotherapy to the pre-operative tumor bed

  • In case of local macroscopic residual disease, patients will be eligible to R-RTx if the following criteria are met:

    1. No evidence of disease progression after HDC/ASCR.
    2. Interval between the last ASCR and radiotherapy start between 60 and 90 days.
    3. Performance status greater or equal 50%.
    4. Hematological status: ANC > 0.5x10^9/L, platelets > 20x10^9/L.
    5. Written informed consent, including agreement of patient or parents/legal guardian for minors, to enter the R-RTx randomization.
    6. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.
    7. Patients should be able and willing to comply with study visits and procedures as per protocol.

In case of parents'/patient's refusal of the randomization, the patient will receive 21.6 Gy radiotherapy to the pre-operative tumor bed

Exclusion Criteria:

Non-inclusion criteria specific to the R-I randomization (RAPID COJEC/GPOH) :

  1. Urinary tract obstruction ≥ grade 3
  2. Heart failure or myocarditis ≥ grade 2, any arrhythmia or myocardial infection
  3. Peripheral motor or sensory neuropathy ≥ grade 3
  4. demyelinating form of Charcot-Marie-Tooth syndrome
  5. hearing impairment ≥ grade 2
  6. Concurrent prophylactic use of phenytoin
  7. cardiorespiratory disease that contraindicates hyperhydration

Non-inclusion criteria common to all randomizations (R-I, R-HDC and R-RTx) :

  1. Any negative answer concerning the inclusion criteria of R-I or R-HDC or R-RTx will render the patient ineligible for the corresponding therapy phase randomization. However, these patients may remain on study and be considered to receive standard treatment of the respective therapy phase, and may be potentially eligible for subsequent randomizations.
  2. Liver function: Alanine aminotransferase (ALT) > 3.0 x ULN and blood bilirubin > 1.5 x ULN (toxicity ≥ grade 2). In case of toxicity ≥ grade 2, call national principal investigator study coordinator to discuss the feasibility.
  3. Renal function: Creatinine clearance and/or GFR < 60 ml/min/1.73m^2 (toxicity ≥ grade 2). If GFR < 60 ml/min/1.73m^2, call national principal investigator to discuss about the treatment
  4. Dyspnea at rest and/or pulse oximetry < 95% in air.
  5. Any uncontrolled intercurrent illness or infection that in the investigator opinion would impair study participation.
  6. Patient under guardianship or deprived of his liberty by a judicial or administrative decision or incapable of giving his consent.
  7. Participating in another clinical study with an IMP while on study treatment.
  8. Concomitant use with yellow fever vaccine and with live virus or bacterial vaccines.
  9. Patient allergic to peanut or soya.
  10. Chronic inflammatory bowel disease and/or bowel obstruction.
  11. Pregnant or breastfeeding women.
  12. Known hypersensitivity to the active substance or to any of the excipients of study drugs known
  13. Concomitant use with St John's Wort (Hypericum Perforatum).

Non-inclusion criteria to R-HDC:

Patients with insufficient metastatic response at the end of induction SIOPEN score > 3 or less than 50% reduction in mIBG score or > 3 bone lesions or less 50% reduction in number of FDG-PET-avid bone lesions for mIBG-non avid tumours, will not be eligible for RHDC

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: phase induction-R-I
R-I: induction regimens RAPID COJEC vs GPOH Assuming a baseline 3-year EFS of 40%, with a sample size of 686 patients (343 in each arm) and a two-sided alpha=5% this trial will have 90% power to demonstrate an improvement of 12% in 3-year EFS, within a recruitment period of 3 years and a minimum follow up of 1.5 years.
Drug: Vincristine
1.5 mg/m^2 (max dose 2 mg)
Other Names:
  • L01CA02
Drug: Carboplatin
750 mg/m^2
Other Names:
  • LO1XA02
Drug: Etoposide
175 mg/m^2
Other Names:
  • L01CB01
Drug: Cyclophosphamide
1050 mg/m^2
Drug: Vindesine
3 mg/m^2/day (max dose 6 mg)
Other Names:
  • L01CA03
Drug: Dacarbazine
200 mg/m^2/day
Other Names:
  • L01AX04
Drug: Ifosfamide
1500 mg/m^2/day
Drug: Doxorubicin
30 mg/m^2/dose
Other Names:
  • L01DB01
Drug: Cisplatin
80 mg/m^2/24h
Drug: Temozolomide 100 MG
100 mg/m²/Day from D0-D4
Other Names:
  • TEMIRI
Drug: Irinotecan
50 mg/m²/jour de J0 à J4
EXPERIMENTAL: Phase high dose chemotherapy consolidation
R-HDC: consolidation regimen Bu-Mel vs Thiotepa + Bu-Mel The 3-year EFS in the Bu-Mel arm (with immunotherapy) is estimated to be 55%. This study aims to show an improvement of 12% for the Thiotepa + Bu-Mel arm (3-year EFS of 67%). With a recruitment of 448 patients (224 in each arm) over a period of 3 years and a minimum follow-up of 2 years, the power to show a 12% difference is 80% (two-sided logrank test and α=5%).
Drug: Busulfan
< 9kg: 1.0 mg/kg/dose 9 kg to < 16 kg : 1.2 mg/kg/dose 16 kg to 23 kg : 1.1 mg/kg/dose >23 kg to 34 kg: 0.95 mg/kg/dose >34 kg: 0.8 mg/kg/dose Infusion IV over 2 hours Administration every 6 hours for a total of 16 doses
Drug: Melphalan
140 mg/m^2/dose IV short infusion (15'), at least 24 h after the last busulfan dose
Other Names:
  • L01AA03
Drug: Thiotepa
300 mg/m^2/day over 2 hours
EXPERIMENTAL: Phase of radiotherapy
R-RTx: 21.6 Gy radiotherapy vs 21.6 Gy + 14.4 Gy boost in patients with macroscopic residual disease
Radiation: Radiotherapy
21.6 Gy 21.6 Gy + boost de 14.4 Gy
Drug: Dinutuximab Beta
Patients >12 kg are dosed based on the BSA: 10 mg/m^2/day Patients ≤ 12 kg are dosed according to their body weight: 0.33 mg/kg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event free survival (EFS)
Time Frame: Assessed at each end of randomization sequences up to one year
Event free survival
Assessed at each end of randomization sequences up to one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 5, 2019

Primary Completion (ANTICIPATED)

November 1, 2026

Study Completion (ANTICIPATED)

November 1, 2032

Study Registration Dates

First Submitted

January 6, 2020

First Submitted That Met QC Criteria

January 6, 2020

First Posted (ACTUAL)

January 9, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 13, 2023

Last Update Submitted That Met QC Criteria

February 10, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-001068-31
  • 2019/2894 (OTHER: CSET number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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