B-NHL 2013, Klinische Studie zur Behandlung von B-NHL und B-AL bei Kindern und Jugendlichen

Primary end point (Data source: WHO)

Primary end point(s): For R1/R2- patients with stage I+II the primary endpoint is event-free survival (EFS_T) defined as time from start of treatment up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.

For R2 patients with stage III disease (the 1st randomized study question) the primary endpoint is event-free survival (EFS_R) defined as time from randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.

For R3/R4 patients (the 2nd randomized study question) the primary endpoints are:
1. Event-free survival (EFS_T/EFS_R) defined as time from start of treatment/randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.
2. Immune reconstitution (IR) rate defined as percentage of patients achieving age adjusted normal B-cell counts 12 months after start of treatment. Achievement of normal B-cell count defined as CD19 positive subpopulations within normal age adjusted range measured in the reference laboratories of the trial.
;Main Objective: Analyzing in pediatric patients (pts)
?the event-free survival (EFS) in pts with very limited B-NHL (R1 and R2 stage I and II) substituting anthracyclines by the rituximab window (R) without compromising survival rates.
?the EFS in pts with limited B-NHL (R2 stage III) randomly assigned to receive R plus standard chemotherapy (S-CTX) or S-CTX without R.
?the EFS and the immune reconstitution (recovery of CD19+ B-cells, IR) in pts with advanced B-NHL/B-AL (R3 and R4 incl. R4 CNS+) treated with BFM-type CTX and randomly assigned schedules of one versus seven doses rituximab. One dose rituximab = R plus S-CTX. Seven doses rituximab = R plus S-CTX with additional six doses of rituximab added to the first four courses of CTX. It will be tested whether EFS can be improved by adding rituximab and whether one dose rituximab is sufficient to achieve the intended improvement of EFS. In addition, the IR will be analyzed comparing the effect of the two regimens of rituximab added to S-CTX.;Secondary Objective: Analyzing
?Event-free survival, overall survival and immune reconstitution for subgroups: histology; CNS status; gender; age: <10 years (y), 10-14 y, >14 y; risk group: R3 versus R4; CD19+ count and/or immunoglobulin (Ig) level prior treatment; Ig substitution; initial performance; response after rituximab window R, after prephase V, after 2nd course; study groups/national groups: BFM versus NOPHO; national groups; and others
?additional parameters for immune reconstitution (IR): lymphocyte subpopulations, Ig levels and grade III/V infections at 6, 12, 18 and 24 months after start of treatment continued 6-monthly until normalization comparing the randomized arms in R3/R4 patients (pts) and evaluating IR in R1/R2 pts. The rate of pts who achieve sufficient titers after vaccination one year after start of treatment will be analyzed
?the effect of one versus seven doses of rituximab on the rate of AE and SAE profile of the randomized arms in R3/R4 pts;Timepoint(s) of evaluation of this end point: ? Interim analysis (intended to be performed 4 years after the first patient in)
? Final analysis (2 years after the end of recruitment period, approximately 2024)