Primary objectiveTo assess the effect of the addition of rituximab in a standard chemotherapy regime on EFS in newly diagnosed PCNSL.Secondary objectiveTo evaluate the effect of the addition of rituximab to a standard chemotherapy regimen with…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Event free survival
Secondary outcome
- Response rates after (R-) MBVP, after cytarabine and after completion of
radiotherapy
- Toxicity
- Overall survival
- Cognitive function and quality of life after treatment
Background summary
For patients with primary central nervous system lymphoma (PCNSL) in a
reasonable or good clinical condition, standard treatment is chemotherapy with
high dose methotrexate (HD-MTX) frequently combined with other chemotherapy
agents. In patients up to 60 years of age this is generally followed by whole
brain radiotherapy. In the Netherlands the MBVP (HD-MTX, BCNU, teniposide,
prednison) schedule is customary in most centres. With this treatment
approximately 30% of patients achieve long-term remission and possibly cure. A
recent randomized study has shown improved survival after the addition of
cytarabine to HD-MTX treatment. Besides this, the incorporation of intravenous
rituximab into the treatment of systemic lymphoma has resulted in a 15-20%
improvement in survival. It is unknown whether rituximab is effective in
PCNSL: the protective blood-brain-barrier may prevent rituximab from reaching
the brain tumor. The effect of rituximab on PCNSL will be investigated in this
study.
Study objective
Primary objective
To assess the effect of the addition of rituximab in a standard chemotherapy
regime on EFS in newly diagnosed PCNSL.
Secondary objective
To evaluate the effect of the addition of rituximab to a standard chemotherapy
regimen with respect to toxicity
Study design
a prospective randomized multicentre (intergroup) phase III study.
Intervention
All patients will be treated with MBVP chemotherapy followed by cytarabine and,
in patients up to 60 years of age, whole brain radiotherapy. In addition,
patients randomized to the investigational arm will be treated with intravenous
rituximab.
Study burden and risks
Intensive treatment with chemotherapy requires several hospital admissions.
This is necessary to safely administer the chemotherapy, to observe the patient
and to monitor side effects. This is common for most intensive treatments in
hematology. Methotrexate can induce renal insufficiency and all chemotherapy
can induce neutropenia and complications of infectious nature
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
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 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
Exclusion criteria
-Evidence of systemic lymphoma
-History of intolerance of exogenous protein administration
-Severe cardiac dysfunction (NYHA classification III-IV, 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)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-014722-42-NL |
| CCMO | NL29231.078.09 |