Methotrexate, Tafasitamab, Lenalidomide and Rituximab in Patients With PCNSL

This is a single-arm, prospective, multicenter, single-stage phase-II trial for patients aged 18-69 years with ECOG PS ≥2 or ≥70 years with previously untreated PCNSL, who are not eligible for HCT-ASCT at investigators decision. This trial evaluates the CRR rate after at least 2 cycles of MTR2, the incidence and severity of adverse events, progression-free survival, and overall survival after one year.

It is planned to enroll eligible patients with PCNSL, i.e. who receive at least 2 cycles of the combination of rituximab, MTX and the IMPs tafasitamab and lenalidomide, over a one-year period. Follow-up will be conducted for 1 year within the trial.

Inclusion criteria

• Age 18-69 years with ECOG PS ≥2 or age ≥70 years, and ineligible for HCT-ASCT as per investigators discretion
• Previously untreated, histologically (or cytologically) confirmed diagnosis of primary B-cell lymphoma of the central nervous system (PCNSL) by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy
• At least one measurable lesion
• Adequate organ function:

• Adequate kidney function, defined as:

• Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 50 ml/min
• Adequate hepatic function, defined as:

• ALAT and ASAT ≤ 3 ULN
• Bilirubin ≤ 2.0 mg/dl (except for Meulengracht disease)
• Adequate bone marrow function, defined as:

• White blood cell (WBC) count ≥ 3000/µL or absolute neutrophil count (ANC) ≥ 1000/µL
• Platelets ≥ 50.000/µL
• Hemoglobin > 8.0 g/dl
• Adequate cardiac function, defined as:

• Cardiac ejection fraction ≥ 40%
• Adequate pulmonary function as per investigators discretion
• Written, signed, and dated informed consent for the trial provided by the participant
• Female persons are eligible to participate if they are post-menopausal or females of no childbearing potential or if they agree to use a method of contraception considered safe described in Section 12.1.2.1.
• Male persons with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods as described in Section 12.1.2.2.

Exclusion criteria

• Prior treatment for PCNSL with the exception of a pre-phase treatment comprising steroid treatment and / or single application of rituximab 375 mg/m² and methotrexate 3.5 g/m²
• Systemic lymphoma manifestation outside the CNS
• Diagnosis of previous Non-Hodgkin lymphoma at any time
• Primary vitreoretinal or leptomeningeal lymphoma without manifestation in the brain parenchyma or spinal cord
• HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and / or presence of RNA confirmed by PCR
• Previous or concurrent malignancies with the following exceptions:

• Surgically cured carcinoma in-situ
• Other kinds of cancer without evidence of disease for at least 5 years
• Hypersensitivity to study treatment or any component of the formulation
• Stomatitis or gastrointestinal ulcerations preventing the use of methotrexate
• Hepatitis B, hepatitis C or hepatitis E infection as determined by PCR
• Severe active infection
• Congenital or acquired immunodeficiency including previous organ transplantation
• Pregnant or nursing (lactating) women.
• Lack of accountability and inability to appreciate the nature, meaning and consequences of the trial and to formulate their own wishes correspondingly
• Non-compliance, for reasons including, but not limited to the following:

• Increased alcohol consumption, drug dependency or substance abuse that would interfere with cooperation with requirements of the trial
• Refusal of blood products during treatment
• Any similar circumstances that appear to make protocol treatment or long-term follow-up impossible
• Relationship of dependence or employer-employee relationship to the sponsor or the investigator