Glucarpidase for the Improvement of Methotrexate Toxicity and Detection in Central Nervous System Involvement of Aggressive Lymphoma

Inclusion Criteria

• Patients must have histologically or cytologically confirmed diagnosis of non-Hodgkin lymphoma and either: * High risk of CNS relapse warranting MTX prophylaxis * Evidence of CNS involvement (either primary central nervous system lymphoma [PCNSL] or secondary CNS lymphoma) warranting therapeutic MTX treatment * Diffuse large B-cell lymphoma (DLBCL) ** Transformation to DLBCL from an antecedent low-grade lymphoma is permitted * Burkitt lymphoma (BL) * Plasmablastic lymphoma * Blastoid variant of mantle cell lymphoma * Richter transformation * Primary CNS lymphoma * Secondary CNS lymphoma of any B cell lineage * B cell non-Hodgkin lymphoma with neurologic symptoms suspicious for CNS involvement
• Patients must have at least one of the following 2 criteria; * Aged >= 65 year with baseline CrCl > 30 ml/min/1.73 m^2 * Any age with a baseline CrCl of 30-59 ml/min/1.73 m^2 * Prior treatment with high dose methotrexate (any dose >= 2 g/m2) containing regimen complicated by prolonged MTX clearance or MTX associated kidney injury
• Patients must meet criteria for and are appropriate candidates for treatment or prophylaxis with high dose systemic MTX of 3.5 g/m^2 if CrCl > 60 ml/min and 2 g/m^2 if creatinine (Cr) 30-59 mL/min
• Patients planned to have 2 or more cycles of high dose MTX as part of treatment regimen. If patents are planned to have more than 4 cycles of MTX, they can be included in study, however glucarpidase will be provided only for up to 4 cycles of MTX
• Patients must be willing and eligible to undergo diagnostic lumbar puncture for initial staging and also post treatment if evidence of CNS involvement
• Patients with confirmed CNS involvement of disease on lumbar puncture testing or those with clinical symptoms of CNS involvement will require baseline and post treatment brain and spinal magnetic resonance imaging (MRI). If there is contraindication to MRI, computed tomography (CT) scan is permitted. * Patients whose lumbar puncture does not show evidence of CNS involvement and ultimately do not proceed onto study treatment may still be enrolled for long-term follow-up and future correlative cfDNA analysis.
• Patients must be willing and able to comply with scheduled visits and testing
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
• Platelets >= 100 x 10^9/L and no platelet transfusion within the past 28 days prior to study registration
• Hemoglobin (Hgb) >= 8g/dL and no red blood cells (RBC) transfusion within the past 28 days prior to study registration
• International normalized ratio (INR) =< 1.5 and partial thromboplastin time (PTT) (activated [a]PTT) =< 1.5 times the upper limit of normal
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the upper limit of normal
• Serum bilirubin =< 1.5 times the upper limit of normal; or total bilirubin =< 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert syndrome
• CrCl >= 30 mL/min using the Cockcroft-Gault equation
• Patients with therapeutically intervenable ascites fluid and/or pleural effusions are permitted on trial. However, patients must demonstrate absent or mild/trace effusion on post procedure imaging with ultrasound or CT scan within 7 days of each MTX cycle
• Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 30 days after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 3 months after the last dose
• Female subjects of childbearing potential must have a negative plasma pregnancy test upon study entry
• Male or female patients ≥ 18 years
• Patients with cognitive impairment due to CNS involvement of disease, as per physician discretion. Physician will document the extent of cognitive impairment and the qualifications of the patient, if applicable * NOTE: After reviewing the consent form, the investigators can use Talk Back to assess comprehension. Questions will be open-ended and should not involve yes or no questions. When there are areas of misunderstanding, the investigator is obligated to review and re-explain that aspect of consent
• Ability for subject (or legally accepted representative, if applicable) to understand and willingness to sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent document
• Subject (or legally acceptable representative, if applicable) signs and dates the written informed consent for the trial prior to the start of any study-specific screening procedures

Exclusion Criteria

• Patients who received CNS directed therapy (intrathecal chemotherapy or systemic HD-MTX) or glucarpidase prior to enrollment. Patients may receive intrathecal prophylaxis at time of initial CSF fluid collection or as part of treatment protocol
• Patients with moderate or severe pleural effusion and/or abdominal ascites at time of enrollment that are not amenable to therapeutic thoracentesis or paracentesis, respectively
• Patients with contraindication or refusal to have cerebrospinal fluid sampling
• Patients with contraindication or refusal to have inpatient HD-MTX administration as part of therapy Patients may not be receiving any other investigational agent
• Patients who will require any medications or substances that are inhibitors or inducers of glucarpidase or MTX during hospitalization for therapy administration are ineligible