Primary CNS lymphoma (PCNSL) accounts for 1 to 2% of all Non-Hodgkin's lymphomas (NHL) and for 2 to 7% of all primary CNS tumors. It's incidence has increased over the past 30 years, particularly in immunocompetent individuals. Over 90% of PCNSL are lymphomas of B-cell origin, accounting to the subtype diffuse large B-cell lymphoma. (DLBCL). Prognosis without treatment resembles that of systemic high-grade NHL, and the median survival of untreated patients with PCNSL is approximately 3 months.
Conditions
Sponsors
Landeshauptstadt Stuttgart, represented by the Executive Medical Director Klinikum Stuttgart
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Immunocompetent patients with newly-diagnosed primary central nervous system B-cell lymphoma 2. Age 18-65 years irrespective of ECOG or 66-70 years (with ECOG Performance Status =2) 3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy 4. Disease exclusively located in the CNS 5. At least one measurable lesion 6. Previously untreated patients (previous or ongoing steroid treatment admitted) 7. Sexually active patients of childbearing potential who agree to take adequate contraceptive measures during study participation 8. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease ADDITIONAL RANDOMIZATION CRITERIA 1. Sufficient stem cell harvest (= 5 x 106 CD34+ cells/kg of body weight) 2. Complete remission, unconfirmed complete remission or partial remission 3. Central pathology results confirming local results 4. Exclusion criterion no. 6 not applicable for re-check for randomization Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 265 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 65
Exclusion criteria
Exclusion criteria: 1. Congenital or acquired immunodeficiency 2. Systemic lymphoma manifestation (outside the CNS) 3. Isolated ocular lymphoma without manifestation in the brain parenchyma or spinal cord 4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years 5. Previous Non-Hodgkin lymphoma at any time 6. Only applicable for patient inclusion (registration) not applicable for re-check for randomization: Inadequate bone marrow (platelet count decreased =CTC grade 1, anemia =CTC grade 1, neutrophil count decreased =CTC grade 1), renal (creatinine clearance 500 ml 13. Hypersensitivity to study treatment or any component of the formulation 14. Taking any medications likely to cause interactions with the study medication 15. Known or persistent abuse of medication, drugs or alcohol 16. Patient without legal capacity and who is unable to understand the nature, significance and consequences of the study and without designated legal representative 17. Persons who are in a relationship of dependency/employment to the sponsor and/ or investigator 18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 19. Concurrent (or planned) pregnancy or lactation 20. Fertile patients refusing to use safe contraceptive methods during the study (for details see clinical trial protocol section 4.3)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy measured as progression-free survival (PFS) of intensive chemotherapy followed by autologous stem-cell transplantation compared to conventional chemotherapy ;Secondary Objective: To compare high-dose chemotherapy followed by autologous stem cell transplantation with optimized conventional chemotherapy regarding OS, treatment response and treatment related morbidities (neurotoxicity and adverse advents) in patients with primary CNS lymphoma. ;Primary end point(s): Primary efficacy endpoint: Progression-free survival (PFS) time from randomization until progression, relapse or death from any cause ;Timepoint(s) of evaluation of this end point: Progression-free survival PFS: Response Assessment III at the end of study treatment (EOT) visit and every imaging diagnostic assessments during follow-up period (for details see protocol intervention scheme, page 19): during year 1-2: every 3 month recommeded for year 3-5: every 6 month recommeded for > year 5 annually or imaging in case of clinical suspicion of disease progression or relapse | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: Efficacy: • Complete response (CR) • Response duration • Overall survival (OS) • Quality of life (QOL): EORTC QLQ-C30 Safety: • (Serious) adverse events • Toxicity • Neurotoxicity (MMSE, EORTC QLQ-BN20, neuropsychological test battery) ;Timepoint(s) of evaluation of this end point: CR will be determined on day 60 after randomization. Response duration observation times for patients where the event of interest was not observed, will be censored at the time last seen alive without the respective event. For overall survival (OS), Quality of life (QLQ), (serious)adverse events (S)AEs, toxicity and neurotoxicity timepoints of evaluation are defined as every assessment during follow up period in accordance with the protocol. year 1-2: every 3 month recommended for year 3-5: every 6 month reccommended for > year 5 annually | — |
Countries
Czechia, Denmark, Germany, Italy, Norway, Switzerland
Contacts
Public ContactElvira Burger, Projektmanagement
Studienzentrum Universitaetsklinikum Freiburg
Outcome results
None listed