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

Overview

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).

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 13, 2017

Interventions

  • 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.
  • 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).

Arms, Groups and Cohorts

  • 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.
  • 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).

Clinical Trial Outcome Measures

Primary Measures

  • Event free survival
    • Time Frame: 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 Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 6 Months

Maximum Age: 17 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Gustave Roussy, Cancer Campus, Grand Paris
  • Collaborator
    • Children’s Oncology Group
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Véronique MINARD, MD, Study Chair, Institut Gustave Roussy, Villejuif, FRANCE
    • Thomas GROSS, MD, Study Chair, Children Oncology Group, USA

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