INTERGROUP TRIAL FOR CHILDREN OR ADOLESCENTS WITH B-CELL NHL OR B-AL: EVALUATION OF RITUXIMAB EFFICACY AND SAFETY IN HIGH RISK PATIENTS

INTERGROUP TRIAL FOR CHILDREN OR ADOLESCENTS WITH B-CELL NHL OR B-AL: EVALUATION OF RITUXIMAB EFFICACY AND SAFETY IN HIGH RISK PATIENTS - Inter-B-NHL ritux 2010

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2010-019224-31-NL

Enrollment

529

Registered

2011-11-30

Start date

2013-02-07

Completion date

Unknown

Last updated

2023-10-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

untreated advanced stage B-cell NHL or B-AL. MedDRA version: 24.0 Level: LLT Classification code 10067070 Term: Follicular B-cell non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10006595 Term: Burkitt's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10067194

Interventions

Trade Name: MabThera Product Name: MabThera Product Code: Ro 45-2294 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: RITUXIMAB CAS Number: 174722-31-7 Current Sponsor c

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: HISTOLOGY AND STAGING DISEASE Phase III study: -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. Phase II study: -Histolo-cytologically proven PMLBL. -PMLBL without CNS involvement. GENERAL CONDITIONS -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. INITIAL WORK-UP -Complete initial work-up within 8 days prior to treatment. OTHERS -Able to comply with scheduled follow-up and with management of toxicity. -Signed informed consent from patients and/or their parents or legal guardians. Are the trial subjects under 18? yes Number of subjects for this age range: 529 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: -Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study. -In phase II study (PMLBL) patients with CNS involvement are not eligible. -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 of less than 7 days deviation in total. -Tumor cell negative for CD20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria) -Prior exposure to rituximab. -Severe active viral infection, especially hepatitis B. Severe infection (such as sepsis, pneumonia, etc..) should be clinically controlled at the time of randomisation. Contact the national co-investigator for further advice if necessary. - Hepatitis B carrier status history of HBV or positive serology

Design outcomes

Primary

Measure	Time frame
Main Objective: Phase III study: For the patients with advanced stage B-cell NHL/B-AL (stage III and LDH > Nx2, any stage IV or B-AL) to test whether adding 6 injections of rituximab to standard LMB chemotherapy regimen improves the EFS compared with LMB chemotherapy alone. November 2015 : the first interim analysis allowed to answer positively Phase II study: To determine the efficacy of DA-EPOCH-R in children and adolescent PMLB in terms of EFS. ;Secondary Objective: In Phase III and phase II studies: -To study the complete remission (CR) rate and the overall survival (OS). -To evaluate safety on all study arms: including toxic deaths, adverse events recorded using the NCI-CTC V4 (non haematological toxicity grade>3, infections grade 3 to 5), cardiac toxicity (CTC grade 2-5 and evolution of left ventricular ejection fraction and left ventricular shortening fraction), number of days with platelets transfusion, number of days with red cells transfusion, rituximab infusion reactions and intensive care unit admission. -To study the rate of patients with Ig (IgM, IgA, IgG) level abnormally low and lymphocyte count abnormally low at 1 year and until 5-year follow-up, and to study the need for immunoglobuline infusions and levels of post (previous and re-)vaccination antibodies at 1 year. ;Primary end point(s): Minimum time to death from any cause, presence of viable cells in residue after 6th DA-EPOCH course, relapse, progressive disease, or second malignancy measured from randomization.;Timepoint(s) of evaluation of this end point: 18 months	—

Measure

Time frame

Main Objective: Phase III study: For the patients with advanced stage B-cell NHL/B-AL (stage III and LDH > Nx2, any stage IV or B-AL) to test whether adding 6 injections of rituximab to standard LMB chemotherapy regimen improves the EFS compared with LMB chemotherapy alone. November 2015 : the first interim analysis allowed to answer positively Phase II study: To determine the efficacy of DA-EPOCH-R in children and adolescent PMLB in terms of EFS. ;Secondary Objective: In Phase III and phase II studies: -To study the complete remission (CR) rate and the overall survival (OS). -To evaluate safety on all study arms: including toxic deaths, adverse events recorded using the NCI-CTC V4 (non haematological toxicity grade>3, infections grade 3 to 5), cardiac toxicity (CTC grade 2-5 and evolution of left ventricular ejection fraction and left ventricular shortening fraction), number of days with platelets transfusion, number of days with red cells transfusion, rituximab infusion reactions and intensive care unit admission. -To study the rate of patients with Ig (IgM, IgA, IgG) level abnormally low and lymphocyte count abnormally low at 1 year and until 5-year follow-up, and to study the need for immunoglobuline infusions and levels of post (previous and re-)vaccination antibodies at 1 year. ;Primary end point(s): Minimum time to death from any cause, presence of viable cells in residue after 6th DA-EPOCH course, relapse, progressive disease, or second malignancy measured from randomization.;Timepoint(s) of evaluation of this end point: 18 months

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Secondary

Measure	Time frame
Secondary end point(s): - Survival (S): Time to death from any cause, measured from the time of randomization - Complete Remission Rate at the assessment time - For group B patients: response in 3 categories: -CR at assessment time (after CYM1) -slow responder = CR at CYVE2 but not after CYM1 -no CR - Acute (at each course) and long term toxicity: toxic deaths, adverse events of NCI-CTC V4 (non haematological toxicity grade>3, infections grade 3 to 5), cardiac toxicity (CTC grade 2-5 and abnormal left ventricular ejection fraction (LV-EF) or abnormal left ventricular shortening fraction (LV-SF)), number of platelets transfusion and of red cells transfusion, intensive care unit admission, rituximab infusion reactions. According to the recommendations of several authors (Steinherz 1992, Kremer-Van Dalen 2006) the cardiotoxicity is defined as following: LV-EF 20 % of baseline for one of these two criteria. - Immune reconstitution assessed by Ig (G, A and M) level and lymphocyte counts at 1 year and every year during follow-up until normal level, post vaccination antibody levels (tetanus, polio, diphtheria, haemophilus influenza and pneumococcus) and need for immunoglobulin infusion. ;Timepoint(s) of evaluation of this end point: it depends on the endpoints (see E.5.2)	—

Measure

Time frame

Secondary end point(s): - Survival (S): Time to death from any cause, measured from the time of randomization - Complete Remission Rate at the assessment time - For group B patients: response in 3 categories: -CR at assessment time (after CYM1) -slow responder = CR at CYVE2 but not after CYM1 -no CR - Acute (at each course) and long term toxicity: toxic deaths, adverse events of NCI-CTC V4 (non haematological toxicity grade>3, infections grade 3 to 5), cardiac toxicity (CTC grade 2-5 and abnormal left ventricular ejection fraction (LV-EF) or abnormal left ventricular shortening fraction (LV-SF)), number of platelets transfusion and of red cells transfusion, intensive care unit admission, rituximab infusion reactions. According to the recommendations of several authors (Steinherz 1992, Kremer-Van Dalen 2006) the cardiotoxicity is defined as following: LV-EF 20 % of baseline for one of these two criteria. - Immune reconstitution assessed by Ig (G, A and M) level and lymphocyte counts at 1 year and every year during follow-up until normal level, post vaccination antibody levels (tetanus, polio, diphtheria, haemophilus influenza and pneumococcus) and need for immunoglobulin infusion. ;Timepoint(s) of evaluation of this end point: it depends on the endpoints (see E.5.2)

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Countries

Australia, Belgium, Canada, France, Hong Kong, Hungary, Italy, Netherlands, Poland, Spain, United Kingdom, United States

Contacts

Public ContactFabienne LEKAIM

InventivHealth

regopseurope@inventivhealth.com+33650093505

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026