None listed
Conditions
Brief summary
Newly diagnosed PCNS lymphoma patients will be randomised to either 2 courses of MBVP or 2 courses of MBVP+Rituximab. All patients will undergo an MRI at the end of chemotherapy and be assessed for consolidation treatment with AraC, after which these patients will undergo another MRI to determine their eligibility or need for WBRT or not. The primary objective of the trial is event free survival.
Interventions
2 courses (4 weeks each) of R-MBVP (Rituximab 375mg/m2 intravenously (i.v), course 1 days 0,7,14,21, course 2 days 0 and 14; methotrexate 3g/m2 iv days 1,15 for all courses; Teniposide 100mg/m2 i.v days 2,3 for all courses; BCNU (Carmustine) 100mg/m2 i.v day 4 for all courses; prednisolone 60mg/m2 orally or i.v days 1-5 for all courses)
Following randomisation to MBVP or R-MBVP, patients will undergo an MRI. Patients with less than a complete response (CR) or partial response (PR) will be remove
2 courses (4 weeks each) of R-MBVP (Rituximab 375mg/m2 intravenously (i.v), course 1 days 0,7,14,21, course 2 days 0 and 14; methotrexate 3g/m2 iv days 1,15 for all courses; Teniposide 100mg/m2 i.v days 2,3 for all courses; BCNU (Carmustine) 100mg/m2 i.v day 4 for all courses; prednisolone 60mg/m2 orally or i.v days 1-5 for all courses) Following randomisation to MBVP or R-MBVP, patients will undergo an MRI. Patients with less than a complete response (CR) or partial response (PR) will be removed from study. Responding patients undergo consolidation with cytarabine (2 g/m2 i.v days 1,2) and have another MRI. Patients greater than or equal to 61 years of age will finish protocol treatment here. Patients with relapse or progressive disease will be withdrawn from study. Patients less than or equal to 60 years of age will undergo whole brain radiotherapy- if CR or (complete remission-unconfirmed) CRu- 20 x 1.5 Gy; if PR 20 x 1.5 Gy and boost 20 x 0.5 Gy. Patients will then have another MRI.
Sponsors
HOVON
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with a histologically confirmed diagnosis of CD20 positive diffuse large B cell lymphoma (DLBCL) based upon a representative histology specimen of brain biopsy according to the world health organisation (WHO) classification; OR 2. Patients with a diagnosis of PCNSL based on magnetic resonance imaging (MRI) evidence of brain parenchymal lesion showing homogeneous contrast enhancement suspect for lymphoma; AND 3. Unequivocal morphological and/or immunophenotypical evidence of cerebrospinal fluid (CSF) CD20 + large cell lymphoma; 4. AND/OR Unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell lymphoma in vitreous fluid; OR 5. Patients with unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell lymphoma in vitreous fluid AND CSF but without a brain parenchymal lesion; 6. Age 18-70 years inclusive; 7. Performance status with or without administration of steroids WHO/Eastern cooperative group (ECOG) 0-3; 8. Written informed consent.
Exclusion criteria
1. Evidence of systemic lymphoma; 2. History of intolerance of exogenous protein administration; 3. Severe cardiac dysfunction (NYHA classification III-IV, , or Left Ventricular Ejection Fraction < 45%) Congestive heart failure or symptomatic coronary artery disease or cardiac arythmias not well controlled with medication ; 4. Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted value); 5. Significant hepatic dysfunction (bilirubin or transaminase greater or equal to 2.5 x upper normal limit) at Screening; 6. Significant renal dysfunction (serum creatinine greater than or equal to 150 micromol/l or clearance < 60 ml/min) at Screening; 7. Presence of third space fluid, such as pleural effusion or ascites; 8. Prior cranial radiotherapy; 9. Active uncontrolled infection; 10. Human immunodeficiency virus (HIV)-positivity; 11. Epstein barr virus (EBV) positive post-transplant lymphoproliferative disorder; 12. Untreated hepatitis B infection (inclusion is possible if adequate antiviral medication e.g. lamivudine or alternative is started and continued for the duration of the trial); 13. Positive pregnancy test in women of reproductive potential; 14. Lactating women; 15. Unable or unwilling to use adequate contraceptive methods (all men, pre-menopausal women) until 12 months after last chemotherapy treatment; 16. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Outcome results
None listed