A Phase I/II Study to Investigate the Use of VORAXAZE™ As Intended Intervention in Patients with CNSL

Inclusion Criteria

• •Primary or secondary CNSL (PCNSL or SCNSL) confirmed by histology or cytology.
• •Renal insufficiency defined as a glomerular filtration rate (GFR, assessed by CKD-EPI or MDRD equation) of 40-80 mL/min or patients with a GFR \>80mL/min who have experienced renal failure, defined as doubling of the serum creatinine compared to the baseline value during a previous HD-MTX treatment.
• •Age ≥ 18 years (male or female).
• •Life expectancy \>3 months.
• •Adequate organ function (i.e., bone marrow, liver, lungs) allowing intensive chemotherapy with MTX.
• •Adequate clinical pathology values:
• •Absolute neutrophil count ≥1.0 x 109/L, hemoglobin ≥9mg/dL (transfusion allowed), platelets ≥100 x 109/L.
• •Total bilirubin ≤1.5x the upper limit of normal except for patients with known Gilbert syndrome.
• •Alanine amino-transferase (ALT) and aspartate amino-transferase (AST) ≤2x the upper limit of normal.
• •Alkaline phosphatase ≤2x the upper limit of normal.
• •Prothrombin time within the normal range for the institution.
• •Signed informed consent by the patient or legal representative prior to start of any study specific procedure.
• •Females of childbearing potential and males must be willing and able to use an adequate method of contraception to avoid pregnancy for the duration of the study in such a manner that the risk of pregnancy is minimized. Acceptable contraceptives include intra-uterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.