OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma

Inclusion Criteria:

1. Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma ofthe central nervous system (PCNSL).
2. Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOGPerformance Status ≤2.
3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by localpathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSFcytology 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. Negative pregnancy test
8. Written informed consent obtained according to international guidelines and local lawsby patient or authorized legal representative in case patient is temporarily legallynot competent due to his or her disease.
9. Ability to understand the nature of the trial and the trial related procedures and tocomply with them.

Exclusion Criteria:

1. Congenital or acquired immunodeficiency including HIV infection and previous organtransplantation.
2. Systemic lymphoma manifestation (outside the CNS).
3. Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinalcord
4. Previous or concurrent malignancies with the exception of surgically cured carcinomain situ of the cervix, carcinoma of the skin or other kinds of cancer without evidenceof disease for at least 5 years.
5. Previous Non-Hodgkin lymphoma at any time.
6. Inadequate renal function (clearance < 60 ml/min).
7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according toinvestigator´s decision
8. Active hepatitis B or C disease.
9. Concurrent treatment with other experimental drugs or participation in aninterventional clinical trial with study medication being administered within the last 30 days before the start of this study.
10. Third space fluid accumulation > 500 ml.
11. Hypersensitivity to study treatment or any component of the formulation.
12. Taking any medications that are likely to cause interactions with the study medication
13. Known or persistent abuse of medication, drugs or alcohol.
14. Active COVID-19-infection or non-compliance with the prevailing hygiene measuresregarding the COVID-19 pandemic
15. Patients without legal capacity who are unable to understand the nature, significanceand consequences of the trial and without designated legal representative.
16. Previous participation in this trial.
17. Persons who are in a relationship of dependency/employment with the sponsor and/or theinvestigator.
18. Any familial, sociological or geographical condition potentially hampering compliancewith the study protocol and follow-up schedule
19. Current or planned pregnancy, nursing period
20. For fertile patients: Failure to use one of the following safe methods ofcontraception: intra-uterine device or hormonal contraception in combination with amechanical method of contraception.