NCT03206671|Active Not RecruitingPhase 3DMC

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

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

University Hospital Muenster ClinicalTrials.gov

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2 other identifiers

UKM12_00202013-003253-21

Study Type

interventional

Target

650

Locations

8 countries

Sites

Timeline

RegisteredJul 2017

StartedAug 2017

CompletionJun 2027

Brief Summary

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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

650

participants targeted

Target at P75+ for phase_3

Timeline

13mo left

Started Aug 2017

Longer than P75 for phase_3

Geographic Reach

8 countries

88 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.8 years study duration

Study Progress89%

Aug 2017Jun 2027

First Submitted

Initial submission to the registry

June 27, 2017

Completed

5 days until next milestone

First Posted

Study publicly available on registry

July 2, 2017

Completed

1 month until next milestone

Study Start

First participant enrolled

August 3, 2017

Completed

9.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2027

Last Updated

April 30, 2026

Status Verified

April 1, 2026

Enrollment Period

9.8 years

First QC Date

June 27, 2017

Last Update Submit

April 29, 2026

Conditions

Mature B-cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

Event-free survival (EFS)
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)
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 Outcomes (13)

Overall survival (OS)
through study completion, maximal seven years
Relapse-free survival (RFS)
through study completion, maximal seven years
Response rate (RR)
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
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
12 months after start of treatment
+8 more secondary outcomes

Study Arms (5)

R1/R2 stage I+II

EXPERIMENTAL

Rituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)

Drug: Rituximab windowDrug: CyclophosphamideDrug: CytarabineDrug: DexamethasoneDrug: EtoposideDrug: IfosfamideDrug: MethotrexateDrug: PrednisoloneDrug: Vincristine

R2 stage III experimental arm

EXPERIMENTAL

Rituximab window + Standard chemotherapy

Drug: Rituximab windowDrug: CyclophosphamideDrug: CytarabineDrug: DexamethasoneDrug: Doxorubicin hydrochlorideDrug: EtoposideDrug: IfosfamideDrug: MethotrexateDrug: PrednisoloneDrug: Vincristine

R2 stage III standard arm

OTHER

Standard chemotherapy

Drug: CyclophosphamideDrug: CytarabineDrug: DexamethasoneDrug: Doxorubicin hydrochlorideDrug: EtoposideDrug: IfosfamideDrug: MethotrexateDrug: PrednisoloneDrug: Vincristine

R3/R4 rituximab plus arm

EXPERIMENTAL

Rituximab window + standard chemotherapy plus six additional doses of rituximab

Drug: Rituximab windowDrug: Additional doses of RituximabDrug: CyclophosphamideDrug: CytarabineDrug: DexamethasoneDrug: Doxorubicin hydrochlorideDrug: Vindesine SulfateDrug: EtoposideDrug: IfosfamideDrug: MethotrexateDrug: PrednisoloneDrug: Vincristine

R3/R4 standard arm

EXPERIMENTAL

Rituximab window + standard chemotherapy

Drug: Rituximab windowDrug: CyclophosphamideDrug: CytarabineDrug: DexamethasoneDrug: Doxorubicin hydrochlorideDrug: Vindesine SulfateDrug: EtoposideDrug: IfosfamideDrug: MethotrexateDrug: PrednisoloneDrug: Vincristine

Interventions

Rituximab windowDRUG

Rituximab window (375 mg/m²)

R1/R2 stage I+IIR2 stage III experimental armR3/R4 rituximab plus armR3/R4 standard arm

Additional doses of RituximabDRUG

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

R3/R4 rituximab plus arm

CyclophosphamideDRUG