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

Primary Purpose

B-cell Non Hodgkin Lymphoma, Mature B-cell Leukemia Burkitt-type

Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
Sponsored by
Gustave Roussy, Cancer Campus, Grand Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Non Hodgkin Lymphoma

Eligibility Criteria

6 Months - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospitals Leuven
  • Children Oncology Group Operations centres
  • The University of Hong Kong (Clinical Trials Centre)
  • Institut de Cancérologie Gustave roussy
  • 2nd Dept. of Pediatrics Semmelweis Univ.
  • Associazione Italiana di Ematologia ed Oncologia Pediatrica
  • Emma Children's Hospital
  • Rectorat of Medical University
  • Sociedad Española de Hematología y Oncología Pediátricas
  • University of Birmingham

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

LMB chemo

LMB chemo + Rituximab

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Survival
Overall survival
Acute toxicity
Acute toxicity during treatment according to NCI-CTC V4
Long term toxicity
Long term toxicity, especially immune reconstitution, cardiac toxicity

Full Information

First Posted
January 19, 2012
Last Updated
June 13, 2017
Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
Children's Oncology Group
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1. Study Identification

Unique Protocol Identification Number
NCT01516580
Brief Title
Intergroup Randomized Trial for Children or Adolescents With B-Cell Non Hodgkin Lymphoma or B-Acute Leukemia: Rituximab Evaluation in High Risk Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
December 2011 (undefined)
Primary Completion Date
June 13, 2017 (Actual)
Study Completion Date
December 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gustave Roussy, Cancer Campus, Grand Paris
Collaborators
Children's Oncology Group

4. Oversight

Data Monitoring Committee
Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Non Hodgkin Lymphoma, Mature B-cell Leukemia Burkitt-type

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
482 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LMB chemo
Arm Type
Active Comparator
Arm Description
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.
Arm Title
LMB chemo + Rituximab
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab, Vincristine, cyclophosphamide, methotrexate, doxorubicin, cytarabine, ara-C
Intervention Description
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).
Primary Outcome Measure Information:
Title
Event free survival
Description
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.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Survival
Description
Overall survival
Time Frame
5 years
Title
Acute toxicity
Description
Acute toxicity during treatment according to NCI-CTC V4
Time Frame
6 months
Title
Long term toxicity
Description
Long term toxicity, especially immune reconstitution, cardiac toxicity
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Véronique MINARD, MD
Organizational Affiliation
Institut Gustave Roussy, Villejuif, FRANCE
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Thomas GROSS, MD
Organizational Affiliation
Children Oncology Group, USA
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospitals Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Children Oncology Group Operations centres
City
Monrovia
Country
Canada
Facility Name
The University of Hong Kong (Clinical Trials Centre)
City
Hong-Kong
Country
China
Facility Name
Institut de Cancérologie Gustave roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
2nd Dept. of Pediatrics Semmelweis Univ.
City
Budapest
ZIP/Postal Code
1094
Country
Hungary
Facility Name
Associazione Italiana di Ematologia ed Oncologia Pediatrica
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Emma Children's Hospital
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Rectorat of Medical University
City
Wroclaw
Country
Poland
Facility Name
Sociedad Española de Hematología y Oncología Pediátricas
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
University of Birmingham
City
Birmingham
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32492302
Citation
Minard-Colin V, Auperin A, Pillon M, Burke GAA, Barkauskas DA, Wheatley K, Delgado RF, Alexander S, Uyttebroeck A, Bollard CM, Zsiros J, Csoka M, Kazanowska B, Chiang AK, Miles RR, Wotherspoon A, Adamson PC, Vassal G, Patte C, Gross TG; European Intergroup for Childhood Non-Hodgkin Lymphoma; Children's Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med. 2020 Jun 4;382(23):2207-2219. doi: 10.1056/NEJMoa1915315.
Results Reference
derived
Links:
URL
http://www.igr.fr
Description
Institute Gustave Roussy web site

Learn more about this trial

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

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