B-cell Non Hodgkin Lymphoma, Mature B-cell Leukemia Burkitt-type
Conditions
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).
Interventions
DRUGVincristine, 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.
DRUGRituximab, 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).
Sponsors
Gustave Roussy, Cancer Campus, Grand Paris
Children's Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Belgium, Canada, China, France, Hungary, Italy, Netherlands, Poland, Spain, United Kingdom
Contacts
STUDY_CHAIRVéronique MINARD, MD
Institut Gustave Roussy, Villejuif, FRANCE
STUDY_CHAIRThomas GROSS, MD
Children Oncology Group, USA
Outcome results
None listed