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

Sponsor
University Hospital Muenster
Study ID
NCT03206671
Phase
PHASE3
Status
Active Not Recruiting

Conditions

  • Mature B-cell Non-Hodgkin Lymphoma

Eligibility Criteria

Sex
ALL
Age
N/A - 18 Years
Healthy Volunteers
Not accepted

Interventions

  • Rituximab window — DRUG
    Rituximab window (375 mg/m²)
  • Additional doses of Rituximab — DRUG
    2 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, 2 doses of Rituximab before the start of the second chemotherapy cycle, 1 dose of rituximab before the start of the third chemotherapy cycle, 1 dose of Rituximab before the start of the forth chemotherapy cycle
  • Cyclophosphamide — DRUG
    see detailed protocol description
  • Cytarabine — DRUG
    see detailed protocol description
  • Dexamethasone — DRUG
    see detailed protocol description
  • Doxorubicin hydrochloride — DRUG
    see detailed protocol description
  • Vindesine Sulfate — DRUG
    see detailed protocol description
  • Etoposide — DRUG
    see detailed protocol description
  • Ifosfamide — DRUG
    see detailed protocol description
  • Methotrexate — DRUG
    see detailed protocol description
  • Prednisolone — DRUG
    see detailed protocol description
  • Vincristine — DRUG
    see detailed protocol description

Study Details

The trial B-NHL 2013 is a collaborative prospective, multi-national, multi-center, randomized trial with participating centers of the NHL-BFM group (Austria, Switzerland, Czech Republic, Germany) and the Scandinavian NOPHO group (Denmark, Finland, Norway, Sweden). The aim of the trial is to evaluate the role of rituximab in the treatment of mature aggressive B-cell Non-Hodgkin lymphoma and leukemia (B-NHL and B-AL) in children and adolescents. The following primary study questions are going to be analyzed: * the effectiveness (event-free survival) in pediatric patients with very limited mature B-NHL (R1 and R2 stage I and II) of substituting anthracyclines by the rituximab window without compromising survival rates. * 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 chemotherapy or standard chemotherapy without the rituximab window. * 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 study questions will address * additional parameters for immune reconstitution, lymphocyte subpopulations, 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 B-NHL/B-AL

Key Dates

Start date
Aug 3, 2017
Status verified
Apr 2026
Primary completion
Jun 30, 2027
Completion
Jun 30, 2027

Study Design

Enrollment
650 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: R1/R2 stage I+II
    Rituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
  • Experimental: R2 stage III experimental arm
    Rituximab window + Standard chemotherapy
  • Other: R2 stage III standard arm
    Standard chemotherapy
  • Experimental: R3/R4 rituximab plus arm
    Rituximab window + standard chemotherapy plus six additional doses of rituximab
  • Experimental: R3/R4 standard arm
    Rituximab window + standard chemotherapy

Primary Outcome Measure

Event-free survival (EFS) [ Time Frame: through study completion, maximal seven years ]

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