Natalizumab for the Treatment of Recurrent, Refractory or Progressive Pulmonary Metastatic Osteosarcoma

Inclusion Criteria

• Subjects may be male or female and must be equal to or greater than 5 years of age but less than or equal to 30 years of age at the time of enrollment. No large studies have evaluated the use of natalizumab in younger pediatric patients, and natalizumab is currently only Food and Drug Administration (FDA) approved for adult use; for this reason, children younger than 5 years of age are excluded from this study
• Subjects must have histologic verification of pOS
• Subjects must have measurable pulmonary disease or pleural disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, documented by clinical, radiographic and histologic criteria, and have progressed, relapsed or become refractory to conventional therapy * Subjects despite having peripheral diseases elsewhere outside of pulmonary disease or pleural disease, may be eligible: * if these diseases have failed upfront standard therapy AND * one or two salvage therapies
• Subjects must have recovered from the acute toxic effects with =< grade 1 as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 of all prior chemotherapy and immunotherapy with the exception of alopecia, anorexia, bone pain, and tumor pain prior to entering this study * Myelosuppressive chemotherapy: Must have adequate recovery of counts from previous treatment prior to entry onto this study * Monoclonal antibodies: At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
• Subjects must have a performance status corresponding to a Karnofsky >= 50% for patients > 16 years of age and Lansky >= 60 for patients =< 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score
• Peripheral absolute neutrophil count (ANC) >= 750/mcL
• Platelet count >= 75,000/mcL (transfusion independent)
• Hemoglobin >= 8.0 g/dL (may receive packed red blood cell transfusions)
• Total bilirubin =< 1.5 times the upper limit of normal for age
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal
• Serum albumin > 2 g/dL
• Ejection fraction of >= 50% by echocardiogram
• Subjects must have the ability to understand and the willingness to sign a written informed consent document if >= 18 years of age and an assent document if < 18 years of age. If < 7 years of age, no assent document is required

Exclusion Criteria

• Patients with evidence of osteosarcoma outside of the lungs or pleura
• Ongoing prior treatment toxicities > grade 1 according to NCI CTCAE version 5.0 with the exception of alopecia, anorexia, bone pain and tumor pain
• Subjects receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to natalizumab
• Subjects currently on immunosuppressive therapy
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, liver failure, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study because natalizumab crosses the placenta and can increase the risk of spontaneous abortion. There is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with natalizumab, therefore breastfeeding should be discontinued if the mother is treated with natalizumab * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained * Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 3 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately * Male patients of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study therapy. Prior history of vasectomy does not replace requirement for contraceptive use
• Human immunodeficiency virus (HIV)-positive subjects and HIV-positive subjects on antiretroviral therapy are ineligible because of the risk for developing a lethal infection when treated with immunosuppressive therapy
• Patients who have or have had progressive multifocal leukoencephalopathy (PML)
• Patients whose pulmonary metastatic disease or pleural disease can be completely surgically resected