Inter-groep studie voor de behandeling van kinderen en adolescenten met een B-cel non-Hodgkin lymfoom of B-ALL: Beoordeling van de werkzaamheid en veiligheid van rituximab bij patiënten met een hoog risico.

Children and adolescents aged until 18 years with untreated advanced stage B-cell NHL or B-AL.



HISTOLOGY AND STAGING DISEASE:

Phase III study:

1. 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;

2. 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.

Phase II study:

1. Histolo-cytologically proven PMLBL;

2. PMLBL without CNS involvement.



GENERAL CONDITIONS:

1. 6 months to less than 18 years of age at the time of consent;

2. 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.



INITIAL WORK-UP:

Complete initial work-up within 8 days prior to treatment.



OTHERS:

1. Able to comply with scheduled follow-up and with management of toxicity;

2. Signed informed consent from patients and/or their parents or legal guardians.

HISTOLOGY AND STAGING DISEASE:

1. Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study;

2. In phase II study (PMLBL) patients with CNS involvement are not eligible.



GENERAL CONDITIONS:

1. Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology;

2. Evidence of pregnancy or lactation period;

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



PRIOR THERAPY:

Past or current anti-cancer treatment except corticosteroids during less than one week.



EXCLUSION CRITERIA RELATED TO RITUXIMAB:

1. Tumor cell negative for CD20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria);

2. Prior exposure to rituximab;

3. Severe active viral infection, especially hepatitis B. Severe infection (such as sepsis, pneumonia, etc..) should be clinically controlled at the time of randomisation. Contact the national co-investigator for further advice if necessary;

4. Hepatitis B carrier status history of HBV or positive serology.