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

Overview[ - collapse ][ - ]

Purpose 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).
ConditionB-cell Non Hodgkin Lymphoma
Mature B-cell Leukemia Burkitt-type
InterventionDrug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
PhasePhase 3
SponsorGustave Roussy, Cancer Campus, Grand Paris
Responsible PartyGustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov IdentifierNCT01516580
First ReceivedJanuary 19, 2012
Last UpdatedNovember 25, 2013
Last verifiedJanuary 2012

Tracking Information[ + expand ][ + ]

First Received DateJanuary 19, 2012
Last Updated DateNovember 25, 2013
Start DateDecember 2011
Estimated Primary Completion DateDecember 2021
Current Primary Outcome MeasuresEvent free survival [Time Frame: 24 months] [Designated as safety issue: No]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.
Current Secondary Outcome Measures
  • Survival [Time Frame: 5 years] [Designated as safety issue: No]Overall survival
  • Acute toxicity [Time Frame: 6 months] [Designated as safety issue: Yes]Acute toxicity during treatment according to NCI-CTC V4
  • Long term toxicity [Time Frame: 5 years] [Designated as safety issue: Yes]Long term toxicity, especially immune reconstitution, cardiac toxicity

Descriptive Information[ + expand ][ + ]

Brief TitleIntergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients
Official TitleIntergroup 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
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).
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • B-cell Non Hodgkin Lymphoma
  • Mature B-cell Leukemia Burkitt-type
InterventionDrug: 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).
Study Arm (s)
  • 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).

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment600
Estimated Completion DateDecember 2021
Estimated Primary Completion DateJune 2019
Eligibility 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.

- 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.
GenderBoth
Ages6 Months
Accepts Healthy VolunteersNo
ContactsContact: Catherine PATTE, MD
33 1 42 11 41 76
catherine.patte@igr.fr
Location CountriesBelgium, France, Hungary, Italy, Netherlands, Spain

Administrative Information[ + expand ][ + ]

NCT Number NCT01516580
Other Study ID NumbersInter B-NHL Ritux 2010 Phase 3
Has Data Monitoring CommitteeYes
Information Provided ByGustave Roussy, Cancer Campus, Grand Paris
Study SponsorGustave Roussy, Cancer Campus, Grand Paris
CollaboratorsChildren's Oncology Group
Investigators Study Chair: Catherine PATTE, MD Institut Gustave Roussy, Villejuif, FRANCEStudy Chair: Thomas GROSS, MD Children Oncology Group, USA
Verification DateJanuary 2012

Locations[ + expand ][ + ]

University Hospitals Leuven
Leuven, Belgium, 3000
Contact: Anne Uyttebroeck, MD | + 32 16 34 39 72 | anne.uyttebroeck@uzleuven.be
Principal Investigator: Anne Uyttebroeck, MD
Recruiting
Institut de Cancérologie Gustave roussy
Villejuif, France, 94805
Contact: Catherine PATTE, MD | catherine.patte@igr.fr
Principal Investigator: Catherine PATTE, MD
Recruiting
2nd Dept. of Pediatrics Semmelweis Univ.
Budapest, Hungary, 1094
Active, not recruiting
Associazione Italiana di Ematologia ed Oncologia Pediatrica
Padova, Italy, 35128
Contact: Angelo Rosolen, MD | + 39 049 821 3579 | angelo.rosolen@unipd.it
Principal Investigator: Angelo rosolen, MD
Recruiting
Emma Children's Hospital
Amsterdam, Netherlands, 1105 AZ
Active, not recruiting
Sociedad Española de Hematología y Oncología Pediátricas
Valencia, Spain, 46010
Contact: Rafael F Delgado, MD | + 34 96 3862624 | Rafael.Fdez-delgado@uv.es
Principal Investigator: Rafael F Delgado, MD
Recruiting