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B-NHL 2013 - Treatment protocol of the NHL-BFM and the NOPHO study groups for mature aggressive B-cell lymphoma and leukemia in children and adolescents - B-NHL 2013

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2013-003253-21-DE

Enrollment

650

Registered

2017-01-03

Start date

2017-05-29

Completion date

Unknown

Last updated

2024-02-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

mature aggressive B-cell lymphoma and leukemia in children and adolescents MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders

Interventions

Pharmaceutical Form: INN or Proposed INN: RITUXIMAB CAS Number: 174722-31-7 Pharmaceutical Form: INN or Proposed INN: CYCLOPHOSPHAMIDE CAS Number: 50-18-0 Pharmaceutical Form: INN or Proposed INN

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • 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 classification. 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 =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: • patients with insufficient work up not allowing a correct stratification into the risk groups • 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.) • 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. • 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 or to ingredients of other IMPs • lack of CD20 expression of the lymphoma cells • pregnancy and lactation

Design outcomes

Primary

Measure	Time frame
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: 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;Primary end point(s): For R1/R2	—

Measure

Time frame

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: 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;Primary end point(s): For R1/R2

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Secondary

Measure	Time frame
Secondary end point(s): For R1/R2 and R3/R4 patients, the secondary endpoints of the trial are • Overall survival (OS_T/OS_R) defined as time from start of treatment/randomization up to death of any cause or to date of last contact for patients alive. • Relapse-free survival (RFS_T/RFS_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. • Response rate (RR) after rituximab window, after prephase and after 2nd course. • Adverse event rate (AE): Rate of patients with acute toxicity defined as grade III/IV/V AE. • Rate of patients achieving normal immunoglobulin level 12 months after start of treatment and the interval to normal immunoglobulin level. • Time interval from start of treatment to normal CD19 positive B-cells in the peripheral blood. • Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment and the interval to normal lymphocyte subpopulations in the peripheral blood. • Rate of infections (defined by CTCAE V4) in the time interval from start of treatment until 24 months after start of treatment and from start of treatment until immune reconstitution (achievement of age adjusted normal B-cell counts). • Rate of patients with sufficient titers after vaccination one year after start of treatment. For R1/R2 patients, an additional secondary endpoint is • Immune reconstitution (IR) rate as defined above in for R3/R4 patients. ;Timepoint(s) of evaluation of this end point: • Final analysis (2 years after the end of recruitment period, approximately 2024)	—

Measure

Time frame

Secondary end point(s): For R1/R2 and R3/R4 patients, the secondary endpoints of the trial are • Overall survival (OS_T/OS_R) defined as time from start of treatment/randomization up to death of any cause or to date of last contact for patients alive. • Relapse-free survival (RFS_T/RFS_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. • Response rate (RR) after rituximab window, after prephase and after 2nd course. • Adverse event rate (AE): Rate of patients with acute toxicity defined as grade III/IV/V AE. • Rate of patients achieving normal immunoglobulin level 12 months after start of treatment and the interval to normal immunoglobulin level. • Time interval from start of treatment to normal CD19 positive B-cells in the peripheral blood. • Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment and the interval to normal lymphocyte subpopulations in the peripheral blood. • Rate of infections (defined by CTCAE V4) in the time interval from start of treatment until 24 months after start of treatment and from start of treatment until immune reconstitution (achievement of age adjusted normal B-cell counts). • Rate of patients with sufficient titers after vaccination one year after start of treatment. For R1/R2 patients, an additional secondary endpoint is • Immune reconstitution (IR) rate as defined above in for R3/R4 patients. ;Timepoint(s) of evaluation of this end point: • Final analysis (2 years after the end of recruitment period, approximately 2024)

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Countries

Austria, Czechia, Czech Republic, Denmark, Finland, Germany, Norway, Sweden, Switzerland

Contacts

Public ContactNHL-BFM study center

Universitätsklinikum Münster

birgit.burkhardt@ukmuenster.de+492518355696

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026

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