B-cell Non Hodgkin LymphomaPhase 3NCT01516580
Intergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients
A Phase 3 study testing Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C and Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C in people with B-cell Non Hodgkin Lymphoma and Mature B-cell Leukemia Burkitt-type, run by Gustave Roussy, Cancer Campus, Grand Paris at 10 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 months to 17 years
- Conditions the study is for
- B-cell Non Hodgkin Lymphoma, Mature B-cell Leukemia Burkitt-type
- What is being tested?
- Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C and Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 482 participants
- Where
- 10 sitesin 10 countries
- Study dates
- Dec 2011to 16 Nov 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
10 sites in 10 countries.
10 sites in 10 countries
Italy1 site
Associazione Italiana di Ematologia ed Oncologia Pediatrica
Padova, 35128
Spain1 site
Sociedad Española de Hematología y Oncología Pediátricas
Valencia, 46010
About this study
Official title: 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).
- Being tested
- Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C, Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
- Medical subject headings
- Lymphoma, B-Cell, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-CDrug
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.
Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-CDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| LMB chemo | Active comparator | 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. Receives: Drug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C |
| LMB chemo + Rituximab | Experimental | 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). Receives: Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (3)
Survival
Overall survival
Measured: 5 years
Acute toxicity
Acute toxicity during treatment according to NCI-CTC V4
Measured: 6 months
Long term toxicity
Long term toxicity, especially immune reconstitution, cardiac toxicity
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startDec 2011
- Primary completion13 Jun 2017
- Study completion16 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for B-cell Non Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 482 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Oncology Group
- Responsible party
- Sponsor
- Investigators
- Véronique MINARD, MD, Study chair, Institut Gustave Roussy, Villejuif, FRANCEThomas GROSS, MD, Study chair, Children Oncology Group, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01516580
- Sponsor's protocol ID
- Inter B-NHL Ritux 2010 Phase 3
- Other IDs
- 2010-019224-31
- Status last verified
- Feb 2026
- First submitted
- 19 Jan 2012
- Last updated
- 9 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37094596Lueza 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.
PubMed 37058173Minard-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.
PubMed 32492302
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01516580
- Acronym / sponsor ID
- Inter B-NHL Ritux 2010 Phase 3
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 482 participants (actual)
- Lead sponsor
- Gustave Roussy, Cancer Campus, Grand ParisUniversity, hospital or other
- Collaborators
- Children's Oncology Group
- Study start
- Dec 2011 (actual)
- Primary completion
- 13 Jun 2017 (actual)
- Study completion
- 16 Nov 2022 (actual)
- First posted
- 25 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LMB chemo | Active comparator | Drug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-CPrephase (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 | Experimental | Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-CLMB 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). |
Who may qualify
- Ages
- 6 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-CPrephase (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 | LMB chemo |
| Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-CLMB 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 | LMB chemo + Rituximab |
Primary outcome
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.
3 secondary outcomes
Survival
Time frame: 5 years
Acute toxicity
Time frame: 6 months
Long term toxicity
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2026.
- Derived from this study: PubMed 37094596Alexander 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.
- Derived from this study: PubMed 37058173Lueza 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.
- Derived from this study: PubMed 32492302Minard-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.
- Institute Gustave Roussy web siteLink provided by the sponsor.
Related trials for B-cell Non Hodgkin Lymphoma
RecruitingPhase 2/3
A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)
B-cell Acute Lymphoblastic Leukemia
Active, not recruitingPhase 1/2
Tafasitamab, Retifanlimab, and Rituximab in Combination With Standard Therapy for the Treatment of Diffuse Large B-cell Lymphoma
Diffuse Large B-Cell Lymphoma, Grade 3b Follicular Lymphoma
RecruitingPhase 2
Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Not yet recruitingPhase 1
A Multicenter, Phase I Study to Evaluate the Feasibility and Safety of Autologous Cytokine-Induced Killer Cells (CIK_D332) in Combination With Tafasitamab and Lenalidomide in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma (DLBCL)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Véronique MINARD, MD study chair
Institut Gustave Roussy, Villejuif, FRANCE
Thomas GROSS, MD study chair
Children Oncology Group, USA
10 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C and Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C in people with B-cell Non Hodgkin Lymphoma and Mature B-cell Leukemia Burkitt-type, run by Gustave Roussy, Cancer Campus, Grand Paris at 10 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Belgium, Canada, China, France, Hungary and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event free survival (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01516580, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2026.