|- candidate number||8230|
|- NTR Number||NTR2427|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||13-jul-2010|
|- Secondary IDs||2009-014722-42 ALLG NHL 24|
|- Public Title||Rituximab in Primary Central Nervous system Lymphoma.
A randomized HOVON / ALLG intergroup study.
|- Scientific Title||Rituximab in Primary Central Nervous system Lymphoma.
A randomized HOVON / ALLG intergroup study.
|- ACRONYM||HOVON 105 PCNSL|
|- hypothesis||The hypothesis to be tested that the outcome in arm B is better than in arm A.|
|- Healt Condition(s) or Problem(s) studied||Primary Central Nervous System Lymphoma (PCNSL)|
|- Inclusion criteria||1. Patients with a histologically confirmed diagnosis of CD20 positive DLBCL based upon a representative histology specimen of brain biopsy according to the WHO classification;|
2. Patients with a diagnosis of PCNSL based on MRI evidence of brain parenchymal lesion showing homogeneous contrast enhancement suspect for lymphoma;
3. Unequivocal morphological and/or immunophenotypical evidence of CSF CD20 + large cell lymphoma;
4. AND/OR Unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell lymphoma in vitreous fluid;
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/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, appendix G, or LVEF < 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 ˇÝ 2.5 x upper normal limit) at Screening;
6. Significant renal dysfunction (serum creatinine ˇÝ150 micromol/l or clearance < 60 ml/min) at Screening;
7. Presence of ˇ°third space fluidˇ±, such as pleural effusion or ascites;
8. Prior cranial radiotherapy;
9. Active uncontrolled infection;
11. (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.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||15-jul-2010|
|- planned closingdate||15-jul-2016|
|- Target number of participants||200|
|- Interventions||In the experimental arm B intravenously administered rituximab will be added to MBVP chemotherapy. Arm A is the standard arm.
The objective of the current study is to investigate whether the addition of intravenous rituximab (375 mg/m^2, 6 gifts in 2 courses) to a standard chemo- and radiotherapy regimen results in improved event-free survival (EFS). As a basis for the treatment the MBVP combination chemotherapy will be used (high-dose metothrexate 3000 mg/m^2 2 gifts per course, teniposide 100 mg/m^2 2 gifts per course, BCNU 100 mg/m^2 1 gift per course, prednisolone 60 mg/m^2 5 gifts per course. Two courses of each 4 weeks will be given. High-dose ARA-C (2000 mg/m^2 q12 hrs for 2 days) will be given as consolidation chemotherapy to patients responding to MBVP before radiotherapy. In patients aged 60 or younger whole brain radiotherapy will be performed (20 x 1.5 Gy)statrting within 4-6 weeks after HD-ARA-C. Intrathecal treatment will be reserved for patients in either arm who exihibit persistent CSF disease after the first two HD-MTX courses, consisting of methotrexate 15 mg twice a week until 2x CSF negative or dexa-methasone 4 mg (or methylprednisolone 25 mg) until 2x CSF negative.
|- Primary outcome||To assess the effect of the addition of rituximab in a standard chemotherapy regime on EFS in newly diagnosed PCNSL.
Event-free survival at 1, 3 and 5 years of all patients defined as failure (relapse, no CR or CRu) or death from any cause.
|- Secondary outcome||To evaluate the effect of the addition of rituximab to a standard chemotherapy regimen with respect to:|
1. Response rates after (R-) MBVP, after HD-Ara-C and after completion of radiotherapy;
2. Toxicity (until 30 days after off protocol treatment);
3. Overall survival;
4. Cognitive function and quality of life after treatment.
|- Timepoints||At entry, before the 2nd, 3rd and 4th HD-MTX, before and after HD-Ara-C, after radiotherapy, during follow-up every 3 (±1) months during the first 2 years, every 6 (±1) months during the next 3 years and annually thereafter.|
|- Trial web site||www.hovon.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Dr. J.K. Doorduijn|
|- CONTACT for SCIENTIFIC QUERIES||Dr. J.K. Doorduijn|
|- Sponsor/Initiator ||Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON), Erasmus Medical Center, Daniel den Hoed Cancer Center |
(Source(s) of Monetary or Material Support)
|Koningin Wilhelmina Fonds (KWF), Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON), Roche Nederland BV|
|- Brief summary||Study phase:|
To assess the effect of the addition of rituximab in a standard chemotherapy regimen on EFS in newly diagnosed PCNSL.
Patients with newly diagnosed PCNSL, age 18-70 years.
Prospective randomized, open label, phase III intergroup study.
Duration of treatment:
Expected duration of 4-5 months.
All patients will be followed until 10 years after randomization.
|- Main changes (audit trail)|
|- RECORD||13-jul-2010 - 5-aug-2010|