Glucarpidase After High-Dose Methotrexate in Patients With Osteosarcoma

Inclusion Criteria: * All races and ethnic groups will be eligible * A minimum of 6 individuals aged \>= 40 years will be enrolled. These participants are considered high-risk. * Eastern Cooperative Oncology Group (ECOG) performance score 0-2. * Participants must have pathologically confirmed diagnosis of osteosarcoma. Participants must be newly diagnosed and previously untreated, although initiation of doxorubicin/cisplatin prior to enrollment is permitted. * Participants must have a recommended treatment plan for their osteosarcoma that includes planned MTX treatment at 8-12 g/m\^2. * Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (or \>= 1.0 x 10\^9/L). * Platelet count 75,000/mm\^3 (or \>= 75 x 10\^9/L). * Hemoglobin \>= 8 g/dL. * Serum creatinine =\< 1.5 x the upper limit of normal (ULN), or glomerular filtration rate (GFR) \>= 60 ml/min/1.73 m\^2 as calculated by the Modification of Diet in Renal Disease (MDRD) formula. * Total serum bilirubin =\< 2 x ULN. * Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =\< 2.5 x ULN. * Participants must be willing to use appropriate contraception for the duration of study treatment and four months after completing HDMTX therapy. * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Malignant disease, other than those being treated in this study. Exceptions to this exclusion include the following: * Malignancies that were treated curatively and hav…