This phase I trial studies how well individualized high dose methotrexate works in treating younger patients with cancer and significant risk for side effects. Individualized high-dose methotrexate may reduce the chances that the level of methotrexate in the blood is too high. When the levels are too high, there may be an increase in side effects. Monitoring and potentially adjusting the final amount of methotrexate given based on the levels of methotrexate in blood samples in the first 24 hours may help prevent side effects in patients with a previous history of side effects from methotrexate or who are at high risk for having side effects.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02076997.
PRIMARY OBJECTIVES:
I. To determine the incidence of successfully achieving peripheral blood concentration of methotrexate of 50-80 uM in patients at high risk of drug toxicity after a 24 hour infusion of high-dose methotrexate treated according to our institutional treatment algorithm for individualized methotrexate dosing.
SECONDARY OBJECTIVES:
I. To determine the incidence of the following side effects in high risk patients receiving high dose methotrexate as a 24 hour infusion: nephrotoxicity, neurotoxicity, mucositis, hepatotoxicity, and myelosuppression.
II. To describe host polymorphisms that may identify risk of methotrexate toxicity or success of this institutional protocol.
III. To describe predictors of successfully achieving an optimum concentration of methotrexate at the end of a 24 hour infusion of high-dose methotrexate (HDMTX) in patients at high risk of drug toxicity treated with this individualized high dose methotrexate protocol.
OUTLINE:
Patients receive high-dose methotrexate intravenously (IV) over 24 hours as determined by their primary provider. Approximately 2 and 6-8 hours after infusion, patients undergo collection of blood samples for the analysis of methotrexate concentrations. At 2 hours, patients with a methotrexate level >= 100 uM stop infusion for 1 hour and then restart methotrexate at a 50% reduction from the infusion rate. At 6 or 8 hours, patients with a methotrexate level >= 75 uM and < 100 uM reduce the infusion rate by 20% and patients with a methotrexate level >= 100 uM stop infusion for 1 hour and then restart at 50% of the most recent infusion rate. Patients with a delay longer than 2 hours will be removed from the study.
After completion of study treatment, patients are followed up every 6-12 months for 2 years.
Lead OrganizationBaylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Principal InvestigatorJennifer Haunani Foster
