Aggressive B-cell NHL MedDRA version: 14.1 Level: PT Classification code 10003902 Term: B-cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10003903 Term: B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Mabthera
Pharmaceutical Form: Concentrate for solution for infusion
Other descriptive name: RITUXIMAB
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: up to
Concentr
Sponsors
HOVON foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligibility criteria for registration, Inclusion criteria R-PECC induction: - Histologically confirmed aggressive B-cell NHL according to the World Health Organization (WHO) classification (see appendix A): Follicular lymphoma grade 3b, Diffuse large B-cell lymphoma - Refractory disease or histologically confirmed first or second relapse (Refractory is defined as no response or partial remission according to CT. Patients in partial response (PR) can only be included in case of positive PET scan or positive biopsy) - CD20 positive (assessed at 1st diagnosis or from fresh histology at confirmation of relapse or immunophenotyping of circulating CD20-positive NHL cells from peripheral blood) - Current measurable disease, i.e. measurable in two perpendicular dimensions on physical examination or computerized tomography (CT) scan using standardized response criteria for NHL (Cheson et al21, 1999) (see appendix B) - Age > 18 years - WHO performance status 0, 1 or 2 (see appendix E) - Life expectancy of at least 3 months - Absolute neutrophil count > 1.5 x 109/l and platelet count > 100 x 109/l (unless caused by NHL infiltration in the bone marrow) - Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: Eligibility criteria for registration, Exclusion criteria R-PECC induction: - Prior allogeneic stem cell transplantation - Prior radioimmunotherapy - Patients who have received chemotherapy or radiotherapy within 6 weeks prior to study entry or who have not recovered from toxicities related to prior therapies - Eligibility for ASCT - ASCT within 12 months of study entry - Investigational drugs within 4 weeks prior to entry on this study or persistent toxic side effects of such therapy - Treatment with external-beam radiation therapy to more than 25% of active bone marrow (see appendix F) - A history of intolerance to rituximab - Severe cardiac, pulmonary, neurological, psychiatric or metabolic disease which could compromise participation in the study, or serious underlying medical conditions which could impair the ability of the patient to participate in the trial - Hepatic dysfunction, bilirubin or transaminases = 2.5 x upper normal limit (unless caused by the NHL) - Renal dysfunction, serum creatinine = 180 µmol/l or clearance = 40 ml/min (unless caused by the NHL) - Active uncontrolled infections - Patients known to be HIV-positive - Current or chronic hepatitis B or hepatitis C infection - Symptomatic NHL localization in the central nervous system (CNS). Lumbal puncture is not required unless CNS involvement with NHL is clinically suspected - Transformed indolent lymphoma - Post-transplant lymphoproliferative disorder - Pregnant or breast-feeding female patients. Negative serum pregnancy test at study is mandatory for female patients of childbearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Final analysis of the primary endpoints will be performed one year after inclusion of the last patient in this trial;Primary end point(s): Feasibility and safety Primary endpoint - The incidence of grade =3 adverse events after treatment with 90Y-ibritumomab tiuxetan. Efficacy Primary endpoint - Failure free survival measured from the start of 90Y-ibritumomab tiuxetan;Main Objective: To assess the feasibility and efficacy of 90Y-ibritumomab tiuxetan consolidation treatment after R-PECC chemotherapy as second or third line treatment in patients with refractory or relapsed aggressive B-cell NHL, after or not eligible for autologous stem cell transplantation. Primary objective: ? Assessment of the feasibility of this treatment approach. Measured primarily by the percentage of patients that reach CR or PR after R-PECC and proceed to 90Y-ibritumomab tiuxetan treatment, and by the fraction of patients that endure the 90Y-ibritumomab tiuxetan treatment without major problems, i.e. the safety and tolerability of 90Y-ibritumomab tiuxetan after R-PECC chemotherapy.;Secondary Objective: Secondary objectives: ? Efficacy of the 90Y-ibritumomab tiuxetan treatment, measured by the fraction of PR PET positive patients who become PET negative after 90Y-ibritumomab tiuxetan treatment and by the failure free survival and overall survival measured from the start of 90Y-ibritumomab tiuxetan. ? Assessment of the results of the whole treatment approach in terms of the overall response rate, duration of response, failure free survival and overall survival from start of R-PECC treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Feasibility and safety: - Incidence and duration of hypoplasia after treatment with 90Y-ibritumomab tiuxetan - Incidence of adverse events (any grade) after treatment with 90Y-ibritumomab tiuxetan - Incidence of adverse events (any grade) after treatment with R-PECC - Percentage of patients treated with R-PECC who proceed to 90Y-ibritumomab tiuxetan treatment Efficacy: - Conversion to PET negative CR after 90Y-ibritumomab tiuxetan treatment of patients who are PET positive before start of 90Y-ibritumomab tiuxetan - Overall survival measured from the start of 90Y-ibritumomab tiuxetan - Response rates to R-PECC and response duration - Failure free survival and overall survival measured from the start of R-PECC;Timepoint(s) of evaluation of this end point: Final analysis of the secondary endpoints will be performed one year after inclusion of the last patient in this trial | — |
Countries
Netherlands
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed