NCT01516580 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2026-02-09

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).

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
maximum Age: 17 Years
minimum Age: 6 Months
sex: ALL
std Ages: CHILD

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
label
LMB chemo
type
ACTIVE_COMPARATOR
description
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).
intervention Names
Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
label
LMB chemo + Rituximab
type
EXPERIMENTAL

interventions

arm Group Labels
LMB chemo
description
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.
name
Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
type
DRUG
arm Group Labels
LMB chemo + Rituximab
description
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).
name
Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 482
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Event free survival
time Frame
24 months

secondary Outcomes

description
Overall survival
measure
Survival
time Frame
5 years
description
Acute toxicity during treatment according to NCI-CTC V4
measure
Acute toxicity
time Frame
6 months
description
Long term toxicity, especially immune reconstitution, cardiac toxicity
measure
Long term toxicity
time Frame
5 years

Full study description

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).

Source references

references

citation
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
37094596
type
DERIVED
citation
Lueza 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
37058173
type
DERIVED
citation
Minard-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
32492302
type
DERIVED