Intergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients
Intergroup Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Evaluation of Rituximab Efficacy and Safety in High Risk Patients - Phase III Trial
2 other identifiers
interventional
482
10 countries
10
Brief Summary
The aim of the trial is to test whether adding 6 injections of rituximab to standard "Lymphome malin B" LMB chemotherapy regimen improves the Event Free Survival (EFS) compared with LMB chemotherapy alone in children / adolescents with advanced stage B-cell Non-Hodgkin Lymphoma (NHL) / B-Acute Leukemia (B-AL)(stage III and LDH \> Nx2, any stage IV or B-AL).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2011
Longer than P75 for phase_3
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2011
CompletedFirst Submitted
Initial submission to the registry
January 19, 2012
CompletedFirst Posted
Study publicly available on registry
January 25, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 13, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 16, 2022
CompletedFebruary 9, 2026
February 1, 2026
5.5 years
January 19, 2012
February 5, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Event free survival
Minimum time to death from any cause, presence of viable cells in residue after \[2nd (Rituximab-)CYVE\], relapse, progressive disease, or second malignancy measured from randomization.
24 months
Secondary Outcomes (3)
Survival
5 years
Acute toxicity
6 months
Long term toxicity
5 years
Study Arms (2)
LMB chemo
ACTIVE COMPARATORPrephase (COP) for all groups followed by: * in group B: 4 courses: 2 COPADM + 2 CYM, with MTX 3g/m² * in group C: 6 courses: 2 COPADM + 2 CYVE + 2 maintenance courses, with MTX 8g/m², in 4h in C1, in 24h in C3 (except the 1st course) and CNS positive patients receive additional IT before each CYVE courses and HDMTX between CYVE courses.
LMB chemo + Rituximab
EXPERIMENTALLMB chemo as in the comparator arm Rituximab 375 mg/m² i.v.: 6 injections: two doses at 48h interval are given at D-2 and D1 of the 2 first courses (COPADM) and one dose at the beginning of the 2 following courses (CYM or CYVE).
Interventions
Prephase (COP) for all groups followed by: in group B: 4 courses: 2 COPADM + 2 CYM, with MTX 3g/m² in group C: 6 courses: 2 COPADM + 2 CYVE + 2 maintenance courses, with MTX 8g/m², in 4h in C1, in 24h in C3 (except the 1st course) and CNS positive patients receive additional IT before each CYVE courses and HDMTX between CYVE courses.
LMB chemo as in the comparator arm Rituximab 375 mg/m² i.v.: 6 injections: two doses at 48h interval are given at D-2 and D1 of the 2 first courses (COPADM) and one dose at the beginning of the 2 following courses (CYM or CYVE).
Eligibility Criteria
You may qualify if:
- Histologically or cytologically proven B-cell malignancies, either Burkitt lymphoma or B-AL (=Burkitt leukaemia = L3-AL) or diffuse large B-cell NHL or aggressive mature B-cell NHL non other specified or specifiable.
- Stage III with elevated LDH level ("B-high"), \[LDH \> twice the institutional upper limit of the adult normal values (\> Nx2)\] or any stage IV or B-AL.
- months to less than 18 years of age at the time of consent.
- Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: during twelve months for women, taking into account the characteristics of rituximab and during five months for men, taking into account the characteristics of methotrexate.
- Complete initial work-up within 8 days prior to treatment that allows definite staging.
- Able to comply with scheduled follow-up and with management of toxicity.
- Signed informed consent from patients and/or their parents or legal guardians
You may not qualify if:
- Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study
- Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology.
- Evidence of pregnancy or lactation period.
- Past or current anti-cancer treatment except corticosteroids during less than one week.
- Tumor cell negative for CD20
- Prior exposure to rituximab.
- Severe active viral infection, especially hepatitis B.
- Hepatitis B carrier status history of HBV or positive serology.
- Participation in another investigational drug clinical trial.
- Patients who, for any reason, are not able to comply with the national legislation.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
University Hospitals Leuven
Leuven, 3000, Belgium
Children Oncology Group Operations centres
Monrovia, Canada
The University of Hong Kong (Clinical Trials Centre)
Hong Kong, China
Institut de Cancérologie Gustave roussy
Villejuif, 94805, France
2nd Dept. of Pediatrics Semmelweis Univ.
Budapest, 1094, Hungary
Associazione Italiana di Ematologia ed Oncologia Pediatrica
Padua, 35128, Italy
Emma Children's Hospital
Amsterdam, 1105 AZ, Netherlands
Rectorat of Medical University
Wroclaw, Poland
Sociedad Española de Hematología y Oncología Pediátricas
Valencia, 46010, Spain
University of Birmingham
Birmingham, United Kingdom
Related Publications (3)
Alexander S, Auperin A, Bomken S, Csoka M, Kazanowska B, Chiang AK, Andres M, Uyttebroeck A, Burke GAA, Zsiros J, Pillon M, Bollard CM, Mussolin L, Verdu-Amoros J, Neven B, Barkauskas DA, Wheatley K, Patte C, Gross TG, Minard-Colin V; Children's Oncology Group; European Intergroup for Childhood Non-Hodgkin's Lymphoma. Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: a prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial. Lancet Haematol. 2023 Jun;10(6):e445-e457. doi: 10.1016/S2352-3026(23)00062-5. Epub 2023 Apr 21.
PMID: 37094596DERIVEDLueza B, Auperin A, Rigaud C, Gross TG, Pillon M, Delgado RF, Uyttebroeck A, Amos Burke GA, Zsiros J, Csoka M, Simonin M, Patte C, Minard-Colin V, Bonastre J. Cost-effectiveness analysis alongside the inter-B-NHL ritux 2010 trial: rituximab in children and adolescents with B cell non-Hodgkin's lymphoma. Eur J Health Econ. 2024 Mar;25(2):307-317. doi: 10.1007/s10198-023-01581-y. Epub 2023 Apr 14.
PMID: 37058173DERIVEDMinard-Colin V, Auperin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM, Zsiros J, Csoka M, Kazanowska B, Chiang AK, Miles RR, Wotherspoon A, Adamson PC, Vassal G, Patte C, Gross TG; European Intergroup for Childhood Non-Hodgkin Lymphoma; Children's Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med. 2020 Jun 4;382(23):2207-2219. doi: 10.1056/NEJMoa1915315.
PMID: 32492302DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Véronique MINARD, MD
Institut Gustave Roussy, Villejuif, FRANCE
- STUDY CHAIR
Thomas GROSS, MD
Children Oncology Group, USA
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 19, 2012
First Posted
January 25, 2012
Study Start
December 1, 2011
Primary Completion
June 13, 2017
Study Completion
November 16, 2022
Last Updated
February 9, 2026
Record last verified: 2026-02