Inclusion Criteria:

- Primary CNS lymphoma diagnosed histologically or by cerebrospinal fluid cytology;
absence of systemic lymphoma manifestations

- Relapse or lymphoma progression after/during high-dose methotrexate containing
first-line chemotherapy or alternative therapy in the case of contraindications
against high-dose methotrexate

- ECOG performance score ≤ 2

- Age ≥18 years and ≤ 75 years

- Life expectancy of at least 3 months

- Absence of active infection

- Negative HIV serology

- Adequate renal function (GFR >30ml/h)

- Adequate bone marrow reserve (neutrophils > 1500/µl, platelets > 80,000/µl)

- Bilirubin <1.5x upper limit of normal (ULN), ALT and AST <3x ULN

- At least 3 weeks interval from prior cytostatic treatment

- Negative pregnancy test

- Patient accessible for treatment and follow-up

- Patient compliance

- Signed informed consent

Exclusion Criteria:

- Secondary CNS lymphoma

- Primary intraocular lymphoma

- Patient eligible for high-dose chemotherapy and autologous stem-cell transplantation

- Concurrent treatment within another clinical trial

- Concurrent other malignant disease

- Symptomatic congestive heart failure (≥NYHA II)

- Active or uncontrolled chronic infection

- Severe concomitant disease incompatible with study conduct

- History of cerebral bleeding

- Concomitant treatment with strong CYP3A4/5-inductors or -inhibitors

- Premenopausal women without highly effective contraception (defined as Pearl index
<1)

- Pregnant or lactating women

- Refusal to record and pass on pseudonymized disease and treatment related data as
part of the treatment protocol

- Concurrent admission to a psychiatric institution by public order