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)

April 29, 2026 updated by: University Hospital Muenster

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Risk group stratification:

R1/R2 stage I+II:

  • R1: resection status: complete
  • R2: resection status: incomplete, stage I and II

R2 III:

- R 2: resection status: incomplete, stage III and LDH < 2 x ULN (according to local reference value for adults)

R3/R4:

  • R3: resection status: incomplete, stage III and LDH ≥ 2 x ULN but < 4 x ULN or stage IV/B-AL and LDH < 4 x ULN and CNS negative
  • R4: resection status: incomplete, Stage III and LDH ≥ 4 x ULN or stage IV/B-AL and LDH ≥ 4 x ULN and CNS negative
  • R4 CNS +: stage IV/B-AL and CNS positive

For patients with very limited disease (R1/R2 stage I/II), the addition of rituximab might allow the omission of anthracyclines without jeopardizing survival rates but reducing acute and long term toxicities. In this treatment arm, it is tested whether the event-free survival is similar to that of the historical control when all patients receive one dose of rituximab as monotherapeutic agent in the rituximab window R five days prior to the start of standard chemotherapy as a substitute for anthracyclines.

For patients with limited disease (R2 stage III) it is tested whether the event-free survival can be improved by adding rituximab to the standard chemotherapy. Two different treatment regimens will be evaluated in a randomized design: Patients in the standard arm will receive the standard chemotherapy. Patients of the rituximab plus arm will receive one dose of rituximab as monotherapeutic agent in the rituximab window R five days prior to the start of standard chemotherapy.

For patients with advanced disease (R3/R4) it is tested whether the event-free survival can be improved by adding rituximab to the standard chemotherapy. Two different rituximab regimens will be evaluated in a randomized design: Patients in the standard arm will receive one dose of rituximab as monotherapeutic agent in the rituximab window R five days prior to the start of standard chemotherapy. Patients of the rituximab plus arm will receive the rituximab window and additional six doses of rituximab added to the first four courses of chemotherapy. In addition the immune reconstitution will be analyzed comparing the effect of the two regimens of rituximab added to standard chemotherapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
650

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
      • Graz, Austria, 8036
        • Univ.Klinik für Kinder- und Jugendheilkunde Graz, Klin. Abteilung für pädiatrische Hämato-Onkologie
      • Innsbruck, Austria, 6020
        • Univ.Klinik für Kinder- und Jugendheilkunde Innsbruck, Universitätsklinik für Pädiatrie I
      • Klagenfurt, Austria, 9020
        • Klinikum Klagenfurt am Wörthersee, Abteilung für Kinder- und Jugendheilkunde
      • Linz, Austria, 4020
        • Kepler Universitätsklinikum, Med Campus IV / Onkologie
      • Salzburg, Austria, 5020
        • LKH Salzburg, Universitätsklinik für Kinder- und Jugendheilkunde, Kinderonkologie
      • Vienna, Austria, 1090
        • St. Anna Kinderspital
  • Czechia
      • Prague, Czechia, 150 06
        • Department of Pediatric Hematology and Oncology, University Hospital Motol
  • Denmark
      • Aalborg, Denmark, 9000
        • Børneonkologisk afsnit 303B, Børneafdelingen, Aalborg Universitetshospital Nord
      • Aarhus, Denmark, 8200 N
        • Børn og Unge afsnit 4, Børneafdelingen, Aarhus Universitetshospital Skejby
      • Copenhagen, Denmark, 2100 Ø
        • Børneonkologisk afsnit 5054, BørneUngeKlinikken, Juliane Marie Centret, Rigshospitalet
      • Odense, Denmark, 5000 C
        • Børneonkologisk afsnit H2, H. C. Andersen Børnehospital, Odense Universitetshospital
  • Finland
      • Helsinki, Finland, 00029 HUS
        • Helsinki University Hospital, Children´s Hospital, Dept of Pediatric Hematology and Oncology
      • Kuopio, Finland, 70029 KYS
        • Kuopio University Hospital, Paediatric Haematology and Oncology
      • Oulu, Finland, 90029 OYS
        • University Hospital of Oulu, Paediatric Haematology and Oncology
      • Tampere, Finland, 33521
        • Tampere University Hospital, Paediatric Haematology and Oncology
      • Turku, Finland, 20521
        • Turku University Hospital, Paediatric and Adolescent Haematology and Oncology
  • Germany
      • Aachen, Germany, 52057
        • Universitätsklinikum Aachen, Klinik für Kinder - und Jugendmedizin, Hämatologie / Onkologie
      • Augsburg, Germany, 86156
        • Klinikum Augsburg, Schwäbisches Kinderkrebszentrum, I. Klinik für Kinder und Jugendliche, Hämatologie / Onkologie
      • Berg, Germany, 13353
        • Charité Campus Virchow-Klinikum, Zentrum für Kinder- und Jugendmedizin, Abt. Hämatologie / Onkologie
      • Berlin, Germany, 13125
        • HELIOS Klinikum Berlin-Buch, Kinderklinik, Pädiatrische Hämatologie und Onkologie
      • Bielefeld, Germany, 33617
        • Evangelisches Krankenhaus Bielefeld GmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie
      • Bonn, Germany, 53113
        • Zentrum für Kinderheilkunde der Universität Bonn, Abt. Päd. Hämatologie / Onkologie
      • Braunschweig, Germany, 38118
        • Städtisches Klinikum Braunschweig gGmbH, Klinik für Kinder- und Jugendmedizin, Station K5 / Päd. Hämato- und Onkologie
      • Bremen, Germany, 28177
        • Klinikum Bremen-Mitte gGmbH, Prof.-Hess-Kinderklinik,Pädiatrische Onkologie und Hämatologie
      • Cologne, Germany, 50924
        • Klinikum der Universität zu Köln, Klinik für Kinder- und Jugendmedizin, Abt. Kinderonkologie und -hämatologie
      • Cottbus, Germany, 03048
        • Carl-Thieme-Klinikum Cottbus gGmbH, Klinik für Kinder- und Jugendmedizin
      • Datteln, Germany, 45711
        • Vestische Kinderklinik, Universität Witten / Herdecke
      • Dortmund, Germany, 44137
        • Klinikum Dortmund gGmbH, Klinik für Kinder- und Jugendmedizin, Station K1, Abt. Päd. Onkologie / Hämatologie
      • Dresden, Germany, 01307
        • Universitätsklinik Carl Gustav Carus der TU Dresden, Klinik für Kinder- und Jugendmedizin
      • Düsseldorf, Germany, 40225
        • Universitätsklinikum Düsseldorf, Zentrum für Kinder- und Jugendmedizin, Klinik für Päd. Hämatologie und Onkologie
      • Erfurt, Germany, 99089
        • HELIOS Klinikum Erfurt GmbH, Klinik für Kinder- und Jugendmedizin, Päd. Onkologie / Hämatologie
      • Erlangen, Germany, 91054
        • Universitätsklinikum Erlangen, Klinik für Kinder- und Jugendmedizin, Pädiatrische Onkologie / Hämatologie
      • Essen, Germany, 45122
        • Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin, Hämatologie / Onkologie
      • Frankfurt am Main, Germany, 60590
        • Universitätsklinikum Frankfurt, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie
      • Freiburg im Breisgau, Germany, 79106
        • Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie
      • Giessen, Germany, 35385
        • Universitätsklinikum Gießen und Marburg, Standort Gießen, Zentrum für Kinderhämatologie und -onkologie
      • Greifswald, Germany, 17475
        • Universitätsklinikum Greifswald KdöR, Klinik und Poliklinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Onkologie und Hämatologie
      • Göttingen, Germany, 37075
        • Georg-August-Universität Universitäts-Kinderklinik, Pädiatrie I
      • Halle, Germany, 06120
        • Universitätsklinikum Halle (Saale), Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg Eppendorf, Zentrum für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie
      • Hanover, Germany, 30625
        • Medizinische Hochschule Hannover, Kinderheilkunde, Päd. Hämatologie / Onkologie
      • Heidelberg, Germany, 69120
        • Universitäts-Kinderklinik Heidelberg, Abt. Hämatologie / Onkologie
      • Herdecke, Germany, 58313
        • Gemeinschaftskrankenhaus Herdecke, Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie
      • Homburg, Germany, 66421
        • Universitätskliniken für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie, Geb. 9
      • Jena, Germany, 07745
        • Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin
      • Karlsruhe, Germany, 76133
        • Städtisches Klinikum Karlsruhe gGmbH, Kinderklinik, Station S 24
      • Kassel, Germany, 34125
        • Klinikum Kassel Gesundheit Nordhessen Holding AG, Klinik für pädiatrische Hämatologie und Onkologie
      • Kiel, Germany, 24105
        • Universitätsklinikum Schleswig Holstein Campus Kiel, Klinik für Allgemeine Pädiatrie, Päd. Onkologie / Hämatologie
      • Koblenz, Germany, 56073
        • Gemeinschaftsklinikum Mittelrhein Kemperhof, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie
      • Krefeld, Germany, 47805
        • HELIOS Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Päd. Hämatologie/Onkologie
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig, Klinik für Kinder und Jugendliche, Abt. Päd. Hämatologie / Onkologie
      • Lübeck, Germany, 23538
        • Universitätsklinikum Schleswig Holstein Campus Lübeck, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie
      • Magdeburg, Germany, 39120
        • Universitätsklinikum Magdeburg A. ö. R., Kinderklinik, Päd. Hämatologie / Onkologie
      • Mainz, Germany, 55101
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie
      • Mannheim, Germany, 68167
        • Klinikum Mannheim gGmbH, Universitäts-Kinderklinik, Päd. Onkologie /Hämatologie
      • Minden, Germany, 32429
        • Johannes Wesling Klinikum Minden, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie, Station E 22
      • München, Germany, 80337
        • Klinikum der LMU, Dr. von Haunersches Kinderspital, Pädiatrische Hämatologie / Onkologie
      • München, Germany, 80804
        • Klinikum Schwabing, Kinderklinik der TU Päd. Hämatologie / Onkologie, Station 24d
      • Münster, Germany, 48149
        • Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie
      • Nuremberg, Germany, 90419
        • Diakonie Neuendettelsau, Kliniken Hallerwiese / Cnopf'sche Kinderklinik, Pädiatrische Hämatologie /Onkologie
      • Oldenburg, Germany, 26133
        • Klinikum Oldenburg AöR, Zentrum für Kinder- und Jugendmedizin, Abt. Hämatologie / Onkologie
      • Regensburg, Germany, 93053
        • Universitätsklinikum Regensburg, Klinik für Kinder- und Jugendmedizin, Abt. Päd. Hämatologie, Onkologie, SZT
      • Rostock, Germany, 18057
        • Universitätsklinikum Rostock, Kinder- und Jugendklinik, Päd. Hämatologie und Onkologie
      • Sankt Augustin, Germany, 53757
        • Asklepios Klinik St. Augustin GmbH, Kinder- und Jugendmedizin, Kinder-Hämatologie und Onkologie
      • Schwerin, Germany, 19049
        • HELIOS Kliniken Schwerin GmbH, Klinik für Kinder- und Jugendmedizin, Station A1
      • Stuttgart, Germany, 70174
        • Klinikum Stuttgart, Olgahospital Zentrum für Kinder- und Jugendmedizin Pädiatrie 5 (Onkologie, Hämatologie, Immunologie)
      • Tübingen, Germany, 72076
        • Universitätsklinik Tübingen Klinik für Kinderheilkunde und Jugendmedizin, Päd. Hämatologie / Onkologie
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie
      • Würzburg, Germany, 97080
        • Universitätskinderklinik Würzburg, Päd. Onkologie und Hämatologie
  • Norway
      • Bergen, Norway, 5021
        • Haukeland University Hospital, National Study Center Norway
      • Oslo, Norway, 0424
        • Oslo University Hospital, Rikshospitalet
      • Tromsø, Norway, 9038
        • University Hospital Northern Norway
      • Trondheim, Norway, 7006
        • St Olavs hospital
  • Sweden
      • Gothenburg, Sweden, 416 85
        • Sahlgrenska Universitetssjukhuset, Drottning Silvias Barn och Ungdomssjukhus, Barncancercentrum
      • Linköping, Sweden, 581 85
        • Universitetssjukhuset i Linköping, Barn och Ungdomsmedicinska kliniken, Barnonkologiska enheten
      • Lund, Sweden, 221 85
        • Skåne Universitetssjukhus, Barnonkologi
      • Stockholm, Sweden, 171 76
        • Karolinska Universitetssjukhuset, Astrid Lindgrens Barnsjukhus, Barnonkologen
      • Umeå, Sweden, 901 85
        • Universitetssjukhus Umeå, Barnonkologiska avdelningen, Barn 3 Norrlands
      • Uppsala, Sweden, 752 39
        • Akademiska sjukhuset, Barnavdelningen för blod- och tumörsjukdomar
  • Switzerland
      • Aarau, Switzerland, 5001
        • Kantonsspital Aarau, Kinderklinik
      • Basel, Switzerland, 4031
        • Universitäts - Kinderspital beider Basel
      • Bellinzona, Switzerland, 6500
        • Ospedale San Giovanni, Reparto die Pediatria
      • Bern, Switzerland, 3010
        • Universitätsklinik für Kinderheilkunde, Pädiatrische Hämatologie/ Onkologie, Inselspital
      • Geneva, Switzerland, 1211
        • Hôpital des Enfants, Unité d'Oncologie Hématologie
      • Lausanne, Switzerland, 1011
        • Centre hospitalier universitaire vaudois, Unité d'hémato-oncologie pédiatrique
      • Lucerne, Switzerland, 6000
        • Kinderspital Pädiatrische Hämatologie/ Onkologie
      • Sankt Gallen, Switzerland, 9006
        • Ostschweizer Kinderspital, Hämatologie/ Onkologie
      • Zurich, Switzerland, 8032
        • Universitäts-Kinderspital, Pädiatrische Onkologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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 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

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 rituximab (MabThera®) or to ingredients of other IMPs.
  • lack of CD20 expression of the lymphoma cells
  • pregnancy and lactation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: R1/R2 stage I+II
Rituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
Drug: Rituximab window
Rituximab window (375 mg/m²)
Drug: Cyclophosphamide
see detailed protocol description
Drug: Cytarabine
see detailed protocol description
Drug: Dexamethasone
see detailed protocol description
Drug: Etoposide
see detailed protocol description
Drug: Ifosfamide
see detailed protocol description
Drug: Methotrexate
see detailed protocol description
Drug: Prednisolone
see detailed protocol description
Drug: Vincristine
see detailed protocol description
Experimental: R2 stage III experimental arm
Rituximab window + Standard chemotherapy
Drug: Rituximab window
Rituximab window (375 mg/m²)
Drug: Cyclophosphamide
see detailed protocol description
Drug: Cytarabine
see detailed protocol description
Drug: Dexamethasone
see detailed protocol description
Drug: Etoposide
see detailed protocol description
Drug: Ifosfamide
see detailed protocol description
Drug: Methotrexate
see detailed protocol description
Drug: Prednisolone
see detailed protocol description
Drug: Vincristine
see detailed protocol description
Drug: Doxorubicin hydrochloride
see detailed protocol description
Other: R2 stage III standard arm
Standard chemotherapy
Drug: Cyclophosphamide
see detailed protocol description
Drug: Cytarabine
see detailed protocol description
Drug: Dexamethasone
see detailed protocol description
Drug: Etoposide
see detailed protocol description
Drug: Ifosfamide
see detailed protocol description
Drug: Methotrexate
see detailed protocol description
Drug: Prednisolone
see detailed protocol description
Drug: Vincristine
see detailed protocol description
Drug: Doxorubicin hydrochloride
see detailed protocol description
Experimental: R3/R4 rituximab plus arm
Rituximab window + standard chemotherapy plus six additional doses of rituximab
Drug: Rituximab window
Rituximab window (375 mg/m²)
Drug: Cyclophosphamide
see detailed protocol description
Drug: Cytarabine
see detailed protocol description
Drug: Dexamethasone
see detailed protocol description
Drug: Etoposide
see detailed protocol description
Drug: Ifosfamide
see detailed protocol description
Drug: Methotrexate
see detailed protocol description
Drug: Prednisolone
see detailed protocol description
Drug: Vincristine
see detailed protocol description
Drug: Doxorubicin hydrochloride
see detailed protocol description
Drug: Additional doses of Rituximab
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
Drug: Vindesine Sulfate
see detailed protocol description
Experimental: R3/R4 standard arm
Rituximab window + standard chemotherapy
Drug: Rituximab window
Rituximab window (375 mg/m²)
Drug: Cyclophosphamide
see detailed protocol description
Drug: Cytarabine
see detailed protocol description
Drug: Dexamethasone
see detailed protocol description
Drug: Etoposide
see detailed protocol description
Drug: Ifosfamide
see detailed protocol description
Drug: Methotrexate
see detailed protocol description
Drug: Prednisolone
see detailed protocol description
Drug: Vincristine
see detailed protocol description
Drug: Doxorubicin hydrochloride
see detailed protocol description
Drug: Vindesine Sulfate
see detailed protocol description

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Event-free survival (EFS)
Time Frame: through study completion, maximal seven years
EFS is 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.
through study completion, maximal seven years
Immune reconstitution rate (only in R3/R4 patients)
Time Frame: 12 months after start of treatment
Immune reconstitution rate is defined as percentage of patients achieving age adjusted normal B-cell counts (CD19 positive subpopulations) 12 months after start of treatment.
12 months after start of treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: through study completion, maximal seven years
OS is defined as time from start of treatment/randomization up to death of any cause or to date of last contact for patients alive.
through study completion, maximal seven years
Relapse-free survival (RFS)
Time Frame: through study completion, maximal seven years
RFS is 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.
through study completion, maximal seven years
Response rate (RR)
Time Frame: after rituximab window on day 5, after prephase (patients with rituximab window on day 10, patients without rituximab window on day 6) and after second course (on an average 5 to 6 weeks after start of treatment)
Complete response, partial remission, objective effect, stable disease or progressive disease
after rituximab window on day 5, after prephase (patients with rituximab window on day 10, patients without rituximab window on day 6) and after second course (on an average 5 to 6 weeks after start of treatment)
Adverse event rate
Time Frame: from the first day of protocol defined treatment until two years after start of protocol defined treatment
Rate of patients with acute toxicity defined as grade III/IV/V AE
from the first day of protocol defined treatment until two years after start of protocol defined treatment
Rate of patients achieving normal immunoglobulin level 12 months after start of treatment
Time Frame: 12 months after start of treatment
12 months after start of treatment
Time interval to normal immunoglobulin level
Time Frame: through study completion, maximal seven years
through study completion, maximal seven years
Time interval from start of treatment to normal CD19 positive B-cells in the peripheral blood.
Time Frame: through study completion, maximal seven years
through study completion, maximal seven years
Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment
Time Frame: 12 months after start of treatment
12 months after start of treatment
Interval to normal lymphocyte subpopulations in the peripheral blood.
Time Frame: through study completion, maximal seven years
through study completion, maximal seven years
Rate of infections (defined by CTCAE V4) in the time interval from start of treatment until 24 months after start of treatment
Time Frame: 24 months after start of treatment
24 months after start of treatment
Rate of infections (defined by CTCAE V4) in the time interval from start of treatment until immune reconstitution (achievement of age adjusted normal B-cell counts)
Time Frame: through study completion, maximal seven years
through study completion, maximal seven years
Rate of patients with sufficient titers after vaccination one year after start of treatment
Time Frame: 1 year after start of treatment
1 year after start of treatment
Immune reconstitution rate (only in R1/R2 patients)
Time Frame: 12 months after start of treatment
Immune reconstitution rate is defined as percentage of patients achieving age adjusted normal B-cell counts (CD19 positive subpopulations) 12 months after start of treatment.
12 months after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Muenster

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Deutsche Krebshilfe e.V., Bonn (Germany)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Birgit Burkhardt, Prof. Dr. Dr., University Hospital Muenster, Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie und Onkologie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 3, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 2, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 30, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UKM12_0020
  • 2013-003253-21 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Medical Conditions

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Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

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