A Study of MabThera (Rituximab) in Primary Central Nervous System Lymphoma.
This study will evaluate the efficacy and safety of MabThera plus high dose methotrexate plus high dose cytarabine in patients with central nervous system non-Hodgkin's lymphoma. Eligible patients will receive a treatment regimen consisting of MabThera (750mg/m2 iv) plus methotrexate (8g/m2 iv) given at intervals up to week 22, plus cytarabine (2g/m2 iv) at week 11 and week 22. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
Drug: rituximab [MabThera/Rituxan]
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Study of the Effect of Rituxan, High Dose Methotrexate and High Dose Cytarabine on Response Rate in Patients With Primary Central Nervous System Lymphoma.|
- Percentage of Participants With a Complete Response (CR) or Unconfirmed CR (CRu) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]CR: complete disappearance of all enhancing abnormalities on contrast-enhanced cranial magnetic resonance imaging (MRI); no evidence of active ocular lymphoma as defined by absence of cells in the vitreous and resolution of any previously documented retinal or optic nerve infiltrates; negative cerebrospinal fluid (CSF) cytology; at the time of CR determination, participant had discontinued use of all corticosteroids for at least 2 weeks. CRu requires fulfillment of CR criteria but with these limitations: Fulfills CR criteria but had continued requirement for corticosteroid therapy at any dose; small but persistent enhancing abnormality on MRI related to biopsy or focal hemorrhage; persistent minor abnormality on follow-up ophthalmologic exam (related to persistent non-malignant cells in vitreous, or alterations in retina/optic nerve not consistent with tumor infiltration) if the abnormality is unlikely to represent ocular lymphoma.
- Percentage of Participants With a CR, CRu or Partial Response (PR) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]PR: greater than or equal to (≥) 50 percent (%) decrease in the contrast-enhancing lesion seen on MRI as compared with the baseline images; (2) Corticosteroid dose was irrelevant to the determination of PR; for participants with ocular disease, ophthalmologic exam must show a decrease in vitreous cell count or retina/optic nerve cellular infiltrate but may have continued to show persistent malignant or suspicious cells; for participants with CSF positive for neoplastic cells, CSF cytology may be negative or continue to show persistent malignant or suspicious cells in patients with ≥50% decrease in the primary brain lesions; no new sites of disease.
- Percentage of Participants With Initial CR or CRu and Subsequent Disease Relapse [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
- Overall Survival [ Time Frame: Time of last follow-up assessment between Day 1 and 3 years ] [ Designated as safety issue: No ]Time from entry into trial until death of any cause. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last dose and participants with no post baseline information were censored at the baseline date.
- Progression-Free Survival (PFS) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]PFS was defined as the time interval between the entry into trial and occurrence of one of the following events: progression of disease (PD) or death as a result of primary central nervous system lymphoma (PCNSL). Participants who were withdrawn from the study without documented progression and for whom there existed case report form (CRF) evidence that evaluations had been made, were censored at the date of last tumor assessment when participant was known to be progression free. Participants without postbaseline tumor assessments but known to be alive were censored at the time of randomization. PD required a ≥25% increase in the contrast-enhanced lesion seen on MRI as compared with baseline or best response (comparison should be made to the smallest of multiple lesions); progression of ocular disease as indicated by an increase in vitreous cell count or progressive retinal or optic nerve infiltration, appearance of any new lesion or site of disease during or at the end of therapy.
|Study Start Date:||September 2007|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Drug: rituximab [MabThera/Rituxan]
750mg/m2 ivDrug: Methotrexate
8g/m2 ivDrug: Cytarabine
Please refer to this study by its ClinicalTrials.gov identifier: NCT00517699
|Greenfield Park, Quebec, Canada, J4V 2H1|
|Quebec City, Quebec, Canada, G1J 1Z4|
|Study Director:||Clinical Trials||Hoffmann-La Roche|