Intergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients

Phase 3

• Conditions: B-cell Non Hodgkin Lymphoma; Mature B-cell Leukemia Burkitt-type
• Interventions: Drug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C; Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C

• Registration Number: NCT01516580
• Lead Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2012-01-19
• Study First Submitted QC: 2012-01-24
• Study First Posted: 2012-01-25
• Status Verified: 2017-06
• Primary Completion: 2017-06-13
• Last Update Submitted: 2017-06-13
• Last Update Posted: 2017-06-14
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 482

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LMB chemo	Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C	Prephase (COP) for all groups followed by: * in group B: 4 courses: 2 COPADM + 2 CYM, with MTX 3g/m² * in group C: 6 courses: 2 COPADM + 2 CYVE + 2 maintenance courses, with MTX 8g/m², in 4h in C1, in 24h in C3 (except the 1st course) and CNS positive patients receive additional IT before each CYVE courses and HDMTX between CYVE courses.
LMB chemo + Rituximab	Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C	LMB chemo as in the comparator arm Rituximab 375 mg/m² i.v.: 6 injections: two doses at 48h interval are given at D-2 and D1 of the 2 first courses (COPADM) and one dose at the beginning of the 2 following courses (CYM or CYVE).

Primary Outcome Measures

Name	Time	Method
Event free survival	24 months	Minimum time to death from any cause, presence of viable cells in residue after \[2nd (Rituximab-)CYVE\], relapse, progressive disease, or second malignancy measured from randomization.

Secondary Outcome Measures

Name	Time	Method
Survival	5 years	Overall survival
Acute toxicity	6 months	Acute toxicity during treatment according to NCI-CTC V4
Long term toxicity	5 years	Long term toxicity, especially immune reconstitution, cardiac toxicity

Trial Locations

Locations (10)

University of Birmingham; 🇬🇧 Birmingham, United Kingdom

University Hospitals Leuven; 🇧🇪 Leuven, Belgium

The University of Hong Kong (Clinical Trials Centre); 🇨🇳 Hong-Kong, China

Children Oncology Group Operations centres; 🇨🇦 Monrovia, Canada

2nd Dept. of Pediatrics Semmelweis Univ.; 🇭🇺 Budapest, Hungary

Institut de Cancérologie Gustave roussy; 🇫🇷 Villejuif, France

Emma Children's Hospital; 🇳🇱 Amsterdam, Netherlands

Associazione Italiana di Ematologia ed Oncologia Pediatrica; 🇮🇹 Padova, Italy

Rectorat of Medical University; 🇵🇱 Wroclaw, Poland

Sociedad Española de Hematología y Oncología Pediátricas; 🇪🇸 Valencia, Spain