B-NHL 2013

Children and adolescents younger than 18 years of age with aggressive mature B-cell Non-Hodgkin lymphoma or leukemia (B-NHL/B-AL)

The trial is a multicenter, non-blinded, randomized, prospective clinical trial.

Primary objectives

• Analyzing the effectiveness (event-free survival) in pediatric patientswith very limited mature B-NHL (R1 and R2 stage I and II) substituting anthracyclines by the rituximab window without
• compromising survival rates.
• Analyzing the effectiveness (event-free survival) in pediatric patients with limited mature B-NHL (R2 stage III) randomly assigned to receive the rituximab window plus standard hemotherapy or standard chemotherapy without the rituximab window.
• Analyzing the effectiveness (event-free survival) and the immune reconstitution (recovery of CD19+ B-cells, IR) in pediatric patients with advanced mature B-NHL/B-AL (R3 and R4 incl. R4 CNS+) treated with BFM-type chemotherapy and randomly assigned schedules of one versus seven doses rituximab.

Secondary objectives

• additional parameters for immune reconstitution, lymphocyte subpopuations, immunoglobulin levels, vaccination titers and infection rates
• kinetics of immune reconstitution after treatment
• adverse event and severe adverse event profile
• inter-individual variability of rituximab response
• role of different mechanisms of action of rituximab in advanced BNHL/B-AL

In patients with very limited disease (R1/R2, stage I+II) the trial assesses non-inferiority of the de-escalated treatment substituting anthracyclines by the rituximab window as compared to the historic control group (HCG) NHL-BFM 95 and B-NHL BFM 04 with standard chemotherapy without rituximab.

In patients with limited disease (R2, stage III) the trial investigates the difference between two treatment arms:

1) intervention (randomized): rituximab window and standard chemotherapy
2) standard chemotherapy without rituximab (randomized)

In patients with advanced disease (R3/R4) the trial investigates the difference between three treatment groups:

1) intervention I (randomized): rituximab window and standard chemotherapy plus six additional doses of rituximab
2) intervention II (randomized): rituximab window and standard chemotherapy
3) historic control group (HCG) NHL-BFM 95 and B-NHL BFM 04: and standard chemotherapy without rituximab

• newly diagnosed aggressive B-NHL or B-AL
• written consent for trial participation, treatment according to theprotocol and consent for data transfer
• follow-up of at least two years after initial diagnosis is expected
• age at diagnosis <18 years

• 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.
• pregnancy and lactation
• any treatment not given according to protocol prior to registration
• overt hepatitis B or history of hepatitis B