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

B-cell Non Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01516580
• Other study ID #: Inter B-NHL Ritux 2010 Phase 3
• Secondary ID: 2010-019224-31
• Status: Active, not recruiting
• Phase: Phase 3
• First received: January 19, 2012
• Last updated: June 13, 2017
• Start date: December 2011
• Est. completion date: December 2021

Study information

• Verified date: June 2017
• Source: Gustave Roussy, Cancer Campus, Grand Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 482
• Est. completion date: December 2021
• Est. primary completion date: June 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Non Hodgkin Lymphoma
• Leukemia
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Mature B-cell Leukemia Burkitt-type

Intervention

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.
• 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).

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven
Canada	Children Oncology Group Operations centres	Monrovia
China	The University of Hong Kong (Clinical Trials Centre)	Hong-Kong
France	Institut de Cancérologie Gustave roussy	Villejuif
Hungary	2nd Dept. of Pediatrics Semmelweis Univ.	Budapest
Italy	Associazione Italiana di Ematologia ed Oncologia Pediatrica	Padova
Netherlands	Emma Children's Hospital	Amsterdam
Poland	Rectorat of Medical University	Wroclaw
Spain	Sociedad Española de Hematología y Oncología Pediátricas	Valencia
United Kingdom	University of Birmingham	Birmingham

Sponsors (2)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris	Children's Oncology Group

Countries where clinical trial is conducted

Belgium,  Canada,  China,  France,  Hungary,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event free survival	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.	24 months
Secondary	Survival	Overall survival	5 years
Secondary	Acute toxicity	Acute toxicity during treatment according to NCI-CTC V4	6 months
Secondary	Long term toxicity	Long term toxicity, especially immune reconstitution, cardiac toxicity	5 years

External Links

•   Institute Gustave Roussy web site