Intergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients

February 5, 2026 updated by: Gustave Roussy, Cancer Campus, Grand Paris

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

482

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

  • Belgium
      • Leuven, Belgium, 3000
        • University Hospitals Leuven
  • Canada
      • Monrovia, Canada
        • Children Oncology Group Operations centres
  • China
      • Hong Kong, China
        • The University of Hong Kong (Clinical Trials Centre)
  • France
      • Villejuif, France, 94805
        • Institut de Cancérologie Gustave Roussy
  • Hungary
      • Budapest, Hungary, 1094
        • 2nd Dept. of Pediatrics Semmelweis Univ.
  • Italy
      • Padua, Italy, 35128
        • Associazione Italiana di Ematologia ed Oncologia Pediatrica
  • Netherlands
      • Amsterdam, Netherlands, 1105 AZ
        • Emma Children's Hospital
  • Poland
      • Wroclaw, Poland
        • Rectorat of Medical University
  • Spain
      • Valencia, Spain, 46010
        • Sociedad Española de Hematología y Oncología Pediátricas
  • United Kingdom
      • Birmingham, United Kingdom
        • University of Birmingham

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

6 months to 17 years (Child)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • 6 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

Exclusion Criteria:

  • 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.
  • There will be no exclusion criteria based on organ function.
  • 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.

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: LMB chemo

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.
Drug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C

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.
Experimental: LMB chemo + Rituximab
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).
Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event free survival
Time Frame: 24 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: 5 years
Overall survival
5 years
Acute toxicity
Time Frame: 6 months
Acute toxicity during treatment according to NCI-CTC V4
6 months
Long term toxicity
Time Frame: 5 years
Long term toxicity, especially immune reconstitution, cardiac toxicity
5 years

Collaborators and Investigators

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

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

Collaborators

Children's Oncology Group

Investigators

  • Study Chair: Véronique MINARD, MD, Institut Gustave Roussy, Villejuif, FRANCE
  • Study Chair: Thomas GROSS, MD, Children Oncology Group, USA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

December 1, 2011

Primary Completion (Actual)

June 13, 2017

Study Completion (Actual)

November 16, 2022

Study Registration Dates

First Submitted

January 19, 2012

First Submitted That Met QC Criteria

January 24, 2012

First Posted (Estimated)

January 25, 2012

Study Record Updates

Last Update Posted (Actual)

February 9, 2026

Last Update Submitted That Met QC Criteria

February 5, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Inter B-NHL Ritux 2010 Phase 3
  • 2010-019224-31 (EudraCT Number)

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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