|- candidate number||12053|
|- NTR Number||NTR3358|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||14-mrt-2012|
|- Secondary IDs||2010-019224-31 / NL37584.018.11; EudraCT / CCMO|
|- Public Title||Inter-groep studie voor de behandeling van kinderen en adolescenten met een B-cel non-Hodgkin lymfoom of B-ALL: Beoordeling van de werkzaamheid en veiligheid van rituximab bij patiŽnten met een hoog risico.|
|- Scientific Title||Intergroup trial for children or adolescents with B-Cell NHL or B-AL: Evaluation of Rituximab efficacy and safety in high risk patients.|
|- ACRONYM||Inter-B-NHL ritux 2010|
|- hypothesis||Rituximab (antiCD20) in association with chemotherapy has extended the survival of adult patients with diffuse large B-cell lymphoma (DLBCL). Also in adults, there is accumulating evidence of a benefit of Rituximab for Primary mediastinal large B-cell lymphoma (PMLBL) patients.|
This large randomized trial is necessary to evaluate whether rituximab can add benefit to the current chemotherapy regimen for childhood B-cell lymphoma and PMLBL.
|- Healt Condition(s) or Problem(s) studied||Childhood PMLBL, Childhood B-cell lymphoma |
|- Inclusion criteria||Children and adolescents aged until 18 years with untreated advanced stage B-cell NHL or B-AL.
HISTOLOGY AND STAGING DISEASE:
Phase III study:
1. 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;
2. Stage III with elevated LDH level (ďB-highĒ), [LDH > twice the institutional upper limit of the adult normal values (> Nx2)] or any stage IV or B-AL.
Phase II study:
1. Histolo-cytologically proven PMLBL;
2. PMLBL without CNS involvement.
1. 6 months to less than 18 years of age at the time of consent;
2. 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.
1. Able to comply with scheduled follow-up and with management of toxicity;
2. Signed informed consent from patients and/or their parents or legal guardians.
|- Exclusion criteria||HISTOLOGY AND STAGING DISEASE:|
1. Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study;
2. In phase II study (PMLBL) patients with CNS involvement are not eligible.
1. Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology;
2. Evidence of pregnancy or lactation period;
3. There will be no exclusion criteria based on organ function.
Past or current anti-cancer treatment except corticosteroids during less than one week.
EXCLUSION CRITERIA RELATED TO RITUXIMAB:
1. Tumor cell negative for CD20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria);
2. Prior exposure to rituximab;
3. Severe active viral infection, especially hepatitis B. Severe infection (such as sepsis, pneumonia, etc..) should be clinically controlled at the time of randomisation. Contact the national co-investigator for further advice if necessary;
4. Hepatitis B carrier status history of HBV or positive serology.
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||19-dec-2011|
|- planned closingdate||1-dec-2021|
|- Target number of participants||640|
|- Interventions||Patients will be randomized to standard treatment or standard treatment with Rituximab. Patients in the intervention group will receive 6 injections of rituximab to a standard LMB chemotherapy regimen. The control group will receive LMB chemotherapy alone.|
|- Primary outcome||Event Free Survival.|
|- Secondary outcome||1. Overall Survival;|
2. Complete Remission Rate at the assessment time;
3. For group B patients: Response in 3 categories:
A. CR at assessment time (after CYM1);
B. Slow responder = CR at CYVE2 but not after CYM1;
C. No CR.
4. Acute (at each course) and long term toxicity;
5. Immune reconstitution.
|- Timepoints||Toxicity will be measured during the study after each course. Interim analyses for efficacy and futility will be performed approximately after 1/3 of EFS events and yearly thereafter.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Drs. M. Mierlo, van|
|- CONTACT for SCIENTIFIC QUERIES||Dr. MD. PhD. J. Zsiros|
|- Sponsor/Initiator ||Institut Gustave Roussy|
(Source(s) of Monetary or Material Support)
|Institut Gustave Roussy, Roche|
|- Brief summary||Phase III - non PMLBL patients:|
Prephase (COP) for all groups followed by:
1. Group B: 4 courses: 2 COPADM + 2 CYM, with MTX 3g/m≤;
2. Group C: 6 courses: 2 COPADM + 2 CYVE + 2 maintenance courses, with MTX 8g/m≤, in 4h in C1, in 24h in C3 (except the 1st course).
Phase II Ė PMLBL patients:
6 courses of DA-EPOCH-R.
Italy, Belgium, UK, Netherlands, Hungary, Poland, Spain, France, North America and Oceani.
(COG will coordinate centers localized in USA, Canada, Australia, New Zealand)
|- Main changes (audit trail)|
|- RECORD||14-mrt-2012 - 5-apr-2012|