This phase II trial studies the effect of glucarpidase in improving methotrexate toxicity and detection in patients with central nervous system involvement of aggressive lymphoma. Patients with aggressive lymphomas who are at high risk of their cancer spreading to the brain and/or spinal cord or are found to have spread to the brain and/or spinal cord are often recommended to receive an additional chemotherapy drug, called methotrexate, as part of their treatment course. High-dose methotrexate is given because it is able to penetrate the brain and spinal cord more effectively than the other standard chemotherapy drugs used for lymphoma. Normally, methotrexate is administered intravenously over 4 hours followed by administration of intravenous fluids and a medication called leucovorin which both help clear the methotrexate from the body. Patients are discharged from the hospital once the methotrexate has cleared and side effects from methotrexate, if any, are resolved or improved. However, patients who are older or have a history of kidney disease are at higher risk for side effects associated with methotrexate and often require a longer time to clear the methotrexate out of the body. Patients who have a prolonged time to clear methotrexate or who have kidney damage caused by methotrexate are candidates to receive an antidote, called glucarpidase (carboxypeptidase G2), which may help to clear methotrexate more quickly form the body.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04668768.
PRIMARY OBJECTIVE:
I. To assess efficacy of glucarpidase in reducing rate of delayed methotrexate (MTX) clearance compared to historical controls in patients that are high risk of delayed clearance and toxicity (age 65 years and older and/or baseline creatinine clearance [CrCl] of 30-59 ml/min) and receiving MTX as part of treatment for or prophylaxis against central nervous system involvement of B cell lymphoma.
SECONDARY OBJECTIVES:
I. To assess the efficacy of glucarpidase in preventing systemic chemotherapy treatment delay.
II. To assess the efficacy of glucarpidase in decreasing complication rate.
III. To assess the pharmacokinetics of MTX clearance after prophylactic glucarpidase administration with standard 2000 unit dosing with each cycle.
IV. To assess the rate of anti-drug antibody detection in patients receiving glucarpidase.
V. To assess the concordance of cell free deoxyribonucleic acid (cfDNA) compared to cell cytology and flow cytometry in the cerebrospinal fluid (CSF).
VI. To describe the rate of central nervous system (CNS) lymphoma clearance in patients with evidence of CNS involvement at baseline who receive glucarpidase.
VII. To describe the rate of CNS relapse in patients receiving prophylactic MTX who receive glucarpidase.
OUTLINE:
Patients receive high-dose methotrexate (HD-MTX) via infusion over 4 hours, then within 24-27 hours, receive glucarpidase intravenously (IV) over 5 minutes. Treatment repeats for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 3 months for 2 years.
Lead OrganizationFox Chase Cancer Center
Principal InvestigatorShazia Nakhoda
