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

Gustave Roussy

Status and phase: Unknown; Phase 3

Conditions: Mature B-cell Leukemia Burkitt-type; B-cell Non Hodgkin Lymphoma

Treatments: Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C; Drug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT01516580

Inter B-NHL Ritux 2010 Phase 3

2010-019224-31 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 482 patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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482 participants in 2 patient groups

LMB chemo

Active Comparator group

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.

Treatment:

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

LMB chemo + Rituximab

Experimental group

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).

Treatment:

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