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

NCT ID: NCT01516580

Last Updated: 2017-06-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

482 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2021-12-31

Brief Summary

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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).

Detailed Description

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Conditions

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B-cell Non Hodgkin Lymphoma Mature B-cell Leukemia Burkitt-type

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C

Intervention Type DRUG

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 + 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).

Group Type EXPERIMENTAL

Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C

Intervention Type DRUG

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).

Interventions

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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.

Intervention Type 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).

Intervention Type DRUG

Eligibility Criteria

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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.
* 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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Oncology Group

NETWORK

Sponsor Role collaborator

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Véronique MINARD, MD

Role: STUDY_CHAIR

Institut Gustave Roussy, Villejuif, FRANCE

Thomas GROSS, MD

Role: STUDY_CHAIR

Children Oncology Group, USA

Locations

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University Hospitals Leuven

Leuven, , Belgium

Site Status

Children Oncology Group Operations centres

Monrovia, , Canada

Site Status

The University of Hong Kong (Clinical Trials Centre)

Hong Kong, , China

Site Status

Institut de Cancérologie Gustave roussy

Villejuif, , France

Site Status

2nd Dept. of Pediatrics Semmelweis Univ.

Budapest, , Hungary

Site Status

Associazione Italiana di Ematologia ed Oncologia Pediatrica

Padua, , Italy

Site Status

Emma Children's Hospital

Amsterdam, , Netherlands

Site Status

Rectorat of Medical University

Wroclaw, , Poland

Site Status

Sociedad Española de Hematología y Oncología Pediátricas

Valencia, , Spain

Site Status

University of Birmingham

Birmingham, , United Kingdom

Site Status

Countries

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Belgium Canada China France Hungary Italy Netherlands Poland Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37094596 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37058173 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32492302 (View on PubMed)

Related Links

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http://www.igr.fr

Institute Gustave Roussy web site

Other Identifiers

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2010-019224-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Inter B-NHL Ritux 2010 Phase 3

Identifier Type: -

Identifier Source: org_study_id

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