Treatment Protocol of the NHL-BFM and the NOPHO Study Groups for Mature Aggressive B-cell Lymphoma and Leukemia in Children and Adolescents

Prior treatment

• participation within a different trial for treatment of B-cell malignancies and/or concurrent treatment within any other clinical trial. Exceptions to this are the NHL-BFM Registry 2012 and trials with different endpoints, involving aspects of supportive treatment which can run parallel to B-NHL 2013 without influencing the outcome of this trial e.g. trials on antiemetics, antibiotics, strategies for psychosocial support etc.

Other illness

• B-cell neoplasia as second malignancy
• any other medical, psychiatric or social condition prohibiting treatment according to the protocol (e.g. previous malignancy, prior organ transplant, HIV infection or AIDS or severe immunodeficiency, etc.)
• overt hepatitis B or history of hepatitis B
• hypersensitivity to rituximab or to murine proteins or to any of the other excipients of the Investigational Medicinal Product rituximab (MabThera®) or to ingredients of other IMPs.

Other

• patients with insufficient work up not allowing a correct stratification into the risk groups
• lack of CD20 expression of the lymphoma cells
• pregnancy and lactation

• Newly diagnosed, histological or cytological and immunological proven aggressive mature B-cell Non-Hodgkin lymphoma including Burkitt lymphoma (BL), Burkitt leukemia (B-AL), diffuse large B-cell lymphoma (DLBCL), or mature B-cell NHL not further classified according to current WHO classification124. For rare subtypes (e.g. primary mediastinal large B-NHL, PMLBL, double hit lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements), consultation of the study center is recommended.
• availability of slides/blocks for reference pathology and international pathology panel (except in cases with immunological and cytomorphological assurance of diagnosis)
• age at diagnosis \< 18 years
• diagnostics and treatment in one of the participating centers of the trial
• no previous chemotherapy, no previous lymphoma-directed treatment. No application of steroids for more than two days during the last month
• adequate hepatic, renal and cardiac function, except if alteration is due to lymphoma infiltration. Please contact the study center in case of unclear cases.
• signed informed consent of patient and/or parents/guardians for treatment according to the protocol, participation and transfer of data
• follow-up of at least two years after initial diagnosis is expected
• Certificate of vaccination against hepatitis B or negative serology, defined as
  • evidence of immunization with HBs-antigen negative, anti-HBs positive and anti-HBc negative or
  • negative hepatitis B serology with HBs-antigen negative, anti-HBs and anti- HBc negative