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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2012 by Gustave Roussy, Cancer Campus, Grand Paris
Sponsor:
Collaborator:
Children's Oncology Group
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier:
NCT01516580
First received: January 19, 2012
Last updated: November 25, 2013
Last verified: January 2012
  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).


Condition Intervention Phase
B-cell Non Hodgkin Lymphoma
Mature B-cell Leukemia Burkitt-type
Drug: Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
Drug: Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gustave Roussy, Cancer Campus, Grand Paris:

Primary Outcome Measures:
  • Event 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.


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


Estimated Enrollment: 600
Study Start Date: December 2011
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   6 Months to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01516580

Contacts
Contact: Catherine PATTE, MD 33 1 42 11 41 76 catherine.patte@igr.fr
Contact: Thomas GROSS, MD 614 722 3552 thomas.gross@nationwidechildrens.org

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

Additional Information:
No publications provided

Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT01516580     History of Changes
Other Study ID Numbers: Inter B-NHL Ritux 2010 Phase 3, 2010-019224-31
Study First Received: January 19, 2012
Last Updated: November 25, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
Rituximab
Doxorubicin
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 29, 2014