Intergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: LMB chemo 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. |
Drug: 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.
|
| Experimental: LMB chemo + Rituximab 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). |
Drug: 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).
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
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.
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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.
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6 months to less than 18 years of age at the time of consent.
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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.
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Complete initial work-up within 8 days prior to treatment that allows definite staging.
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Able to comply with scheduled follow-up and with management of toxicity.
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Signed informed consent from patients and/or their parents or legal guardians
Exclusion Criteria:
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Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study
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Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology.
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Evidence of pregnancy or lactation period.
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There will be no exclusion criteria based on organ function.
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Past or current anti-cancer treatment except corticosteroids during less than one week.
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Tumor cell negative for CD20
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Prior exposure to rituximab.
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Severe active viral infection, especially hepatitis B.
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Hepatitis B carrier status history of HBV or positive serology.
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Participation in another investigational drug clinical trial.
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Patients who, for any reason, are not able to comply with the national legislation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospitals Leuven | Leuven | Belgium | 3000 | |
| 2 | Children Oncology Group Operations centres | Monrovia | Canada | ||
| 3 | The University of Hong Kong (Clinical Trials Centre) | Hong-Kong | China | ||
| 4 | Institut de Cancérologie Gustave roussy | Villejuif | France | 94805 | |
| 5 | 2nd Dept. of Pediatrics Semmelweis Univ. | Budapest | Hungary | 1094 | |
| 6 | Associazione Italiana di Ematologia ed Oncologia Pediatrica | Padova | Italy | 35128 | |
| 7 | Emma Children's Hospital | Amsterdam | Netherlands | 1105 AZ | |
| 8 | Rectorat of Medical University | Wroclaw | Poland | ||
| 9 | Sociedad Española de Hematología y Oncología Pediátricas | Valencia | Spain | 46010 | |
| 10 | University of Birmingham | Birmingham | United Kingdom |
Sponsors and Collaborators
- Gustave Roussy, Cancer Campus, Grand Paris
- Children's Oncology Group
Investigators
- Study Chair: Véronique MINARD, MD, Institut Gustave Roussy, Villejuif, FRANCE
- Study Chair: Thomas GROSS, MD, Children Oncology Group, USA
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- Inter B-NHL Ritux 2010 Phase 3
- 2010-019224-31