Clinical trial NCT01516580: Intergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients
Official title: Intergroup Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Evaluation of Rituximab Efficacy and Safety in High Risk Patients - Phase III Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: B-cell Non Hodgkin Lymphoma
Mature B-cell Leukemia Burkitt-type
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
Collaborators: name: Children's Oncology Group
First posted: 2012-01-25
Enrollment: 482
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the trial is to test whether adding 6 injections of rituximab to standard "Lymphome malin B" LMB chemotherapy regimen improves the Event Free Survival (EFS) compared with LMB chemotherapy alone in children / adolescents with advanced stage B-cell Non-Hodgkin Lymphoma (NHL) / B-Acute Leukemia (B-AL)(stage III and LDH \> Nx2, any stage IV or B-AL).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically proven B-cell malignancies, either Burkitt lymphoma or B-AL (=Burkitt leukaemia = L3-AL) or diffuse large B-cell NHL or aggressive mature B-cell NHL non other specified or specifiable.
* Stage III with elevated LDH level ("B-high"), \[LDH \> twice the institutional upper limit of the adult normal values (\> Nx2)\] or any stage IV or B-AL.
* 6 months to less than 18 years of age at the time of consent.
* Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: during twelve months for women, taking into account the characteristics of rituximab and during five months for men, taking into account the characteristics of methotrexate.
* Complete initial work-up within 8 days prior to treatment that allows definite staging.
* Able to comply with scheduled follow-up and with management of toxicity.
* Signed informed consent from patients and/or their parents or legal guardians

Exclusion Criteria:

* Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study
* Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology.
* Evidence of pregnancy or lactation period.
* There will be no exclusion criteria based on organ function.
* Past or current anti-cancer treatment except corticosteroids during less than one week.
* Tumor cell negative for CD20
* Prior exposure to rituximab.
* Severe active viral infection, especially hepatitis B.
* Hepatitis B carrier status history of HBV or positive serology.
* Participation in another investigational drug clinical trial.
* Patients who, for any reason, are not able to comply with the national legislation.

Primary outcomes:
measure: Event free survival
timeFrame: 24 months
Secondary outcomes:
measure: Survival
timeFrame: 5 years
measure: Acute toxicity
timeFrame: 6 months
measure: Long term toxicity
timeFrame: 5 years
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Monrovia
country: Canada
facility: Children Oncology Group Operations centres
city: Hong-Kong
country: China
facility: The University of Hong Kong (Clinical Trials Centre)
city: Villejuif
country: France
facility: Institut de Cancérologie Gustave roussy
city: Budapest
country: Hungary
facility: 2nd Dept. of Pediatrics Semmelweis Univ.
city: Padova
country: Italy
facility: Associazione Italiana di Ematologia ed Oncologia Pediatrica
city: Amsterdam
country: Netherlands
facility: Emma Children's Hospital
city: Wroclaw
country: Poland
facility: Rectorat of Medical University
city: Valencia
country: Spain
facility: Sociedad Española de Hematología y Oncología Pediátricas
city: Birmingham
country: United Kingdom
facility: University of Birmingham
Study officials:
affiliation: Institut Gustave Roussy, Villejuif, FRANCE
name: Véronique MINARD, MD
role: STUDY_CHAIR
affiliation: Children Oncology Group, USA
name: Thomas GROSS, MD
role: STUDY_CHAIR
References:
citation: Minard-Colin V, Auperin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM, Zsiros J, Csoka M, Kazanowska B, Chiang AK, Miles RR, Wotherspoon A, Adamson PC, Vassal G, Patte C, Gross TG; European Intergroup for Childhood Non-Hodgkin Lymphoma; Children's Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med. 2020 Jun 4;382(23):2207-2219. doi: 10.1056/NEJMoa1915315.