E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Central Nervous system Lymphoma |
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E.1.1.1 | Medical condition in easily understood language |
Lymphoma of the Central Nervous System |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036685 |
E.1.2 | Term | Primary central nervous system lymphoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess the effect of the addition of rituximab to standard chemotherapy for PCNSL |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of the addition of rituximab to a standard chemotherapy regimen with respect to toxicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with a histologically confirmed diagnosis of CD20 positive DLBCL based upon a representative histology specimen of brain biopsy according to the WHO/ECOG classification
OR
Patients with a diagnosis of PCNSL based on MRI evidence of brain parenchymal lesion showing homogeneous contrast enhancement suspect for lymphoma
AND unequivocal morphological and/or immunophenotypical evidence of CSF CD20 + large cell lymphoma AND/OR unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell lymphoma in vitreous fluid
OR
Patients with unequivocal morphological and/or immunophenotypical evidence of CD20 + large cell lymphoma in vitreous fluid AND CSF but without a brain parenchymal lesion
-Age 18-70 years inclusive
-Performance status with or without administration of steroids WHO 0 – 3
-Written informed consent
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E.4 | Principal exclusion criteria |
-Evidence of systemic lymphoma
-History of intolerance of exogenous protein administration
-Severe cardiac dysfunction (NYHA classification III-IV, appendix H, or LVEF < 45%) Congestive heart failure or symptomatic coronary artery disease or cardiac arythmias not well controlled with medication
-Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted value)
-Significant hepatic dysfunction (bilirubin or transaminase ≥ 2.5 x upper normal limit).
-Significant renal dysfunction (serum creatinine ≥150 umol/l or clearance < 60 ml/min
-Presence of “third space fluid”, such as pleural effusion or ascites
-Prior cranial radiotherapy
-Active uncontrolled infection
-HIV-positivity
-(EBV positive) post-transplant lymphoproliferative disorder
-Untreated hepatitis B infection (inclusion is possible if adequate antiviral medication e.g. lamivudine or alternative is started)
-Positive pregnancy test in women of reproductive potential
-Lactating women
-Unable or unwilling to use adequate contraceptive methods (all men, pre-menopausal women)
-Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
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E.5 End points |
E.5.1 | Primary end point(s) |
Event-free survival measured from the date of registration. Patients without event (an event is no CR(u) on protocol, relapse or death in CR(u)) are censored at the last day they were known to be alive. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At entry, before second MBVP, before HD-Ara-C, after HD-Ara-C, after radiotherapy, during FU until relapse/progression |
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E.5.2 | Secondary end point(s) |
- Response rates after (R-)MBVP, after HD-Ara-C and after completion of radiotherapy
- Toxicity
- Overall survival measured from the date of registration. Patients still alive or lost to follow up are censored at the last day they were known to be alive.
- Cognitive function and quality of life after treatment
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At entry, before second MBVP, before HD-Ara-C, after HD-Ara-C, after radiotherapy, during FU until relapse/progression |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
chemotherapy without Rituximab |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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At 2 years after the randomization of the finally enrolled patients. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |