Modified Immune Cells (GD2 Specific Chimeric Antigen Receptor and IL-15 Expressing Autologous Natural Killer T-Cells) with or without Etanercept in Treating Children with Relapsed or Refractory Neuroblastoma

Inclusion Criteria

• PROCUREMENT: Relapsed or refractory high-risk neuroblastoma.
• PROCUREMENT: Life expectancy of at least 12 weeks.
• PROCUREMENT: Karnofsky/Lansky score of 60% or greater.
• PROCUREMENT: Absence of human anti-mouse antibodies (HAMA) prior to enrollment (only in patients that have been previously treated with murine antibodies).
• PROCUREMENT: Ability to tolerate leukocyte apheresis.
• PROCUREMENT: Informed consent and assent (as applicable) obtained from parent/guardian and child.
• PROCUREMENT: Absolute neutrophil count (ANC) >= 500/ul. * ANC >= 500 without the use granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) for at least 48 hours (hrs).
• PROCUREMENT: Platelet count >= 20,000/ul. * Patients may be transfused to obtain a platelet count >= 20,000/ul.
• PROCUREMENT: Pulse oxygen (Ox) >= 90% on room air.
• PROCUREMENT: Serum aspartate aminotransferase (AST) less than 3 times the upper limit of normal.
• PROCUREMENT: Total bilirubin less than 1.5 times the upper limit of normal.
• PROCUREMENT: Creatinine < 1.5 upper limit of normal.
• PROCUREMENT: Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician’s assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
• PROCUREMENT: Weight greater than 12 kg.
• PROCUREMENT: Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to the procurement.
• TREATMENT: Relapsed or refractory high risk neuroblastoma.
• TREATMENT: Life expectancy of at least 12 weeks.
• TREATMENT: Karnofsky/Lansky score of 60% or greater.
• TREATMENT: Patients must have an ANC >= 500/ul (within 10 days prior to initiation of study related treatment). * ANC >= 500 without the use G-CSF or GM-CSF for at least 48 hrs.
• TREATMENT: Platelet count >= 20,000/ul (within 10 days prior to initiation of study related treatment). * Patients may be transfused to obtain a platelet count >= 20,000/ul.
• TREATMENT: Pulse Ox >= 90% on room air (within 10 days prior to initiation of study related treatment).
• TREATMENT: Serum AST less than 3 times the upper limit of normal (within 10 days prior to initiation of study related treatment).
• TREATMENT: Total bilirubin less than 1.5 times the upper limit of normal (within 10 days prior to initiation of study related treatment).
• TREATMENT: Creatinine < 1.5 upper limit of normal (within 10 days prior to initiation of study related treatment).
• TREATMENT: Recovered from the acute toxic effects of all prior chemotherapy based on the enrolling physician’s assessment (if some effects of chemotherapy are expected to last long term, patient is eligible if meeting other eligibility criteria).
• TREATMENT: Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies.
• TREATMENT: Patients must have autologous transduced NKTs with >= 20% expression of GD2-specific CAR.
• TREATMENT: Informed consent and assent (as applicable) obtained from parent/guardian and child.
• TREATMENT: Weight greater than 12 kg.
• TREATMENT: Negative QuantiFERON-TB or T-SPOT testing within 3 months prior to the start of lymphodepletion (LD).

Exclusion Criteria

• PROCUREMENT: Rapidly progressive disease.
• PROCUREMENT: History or hypersensitivity to murine protein-containing products.
• PROCUREMENT: Tumor causing airway obstruction.
• PROCUREMENT: Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine. * Patients may receive treatment if treated with corticosteroids with dose of less than 0.5 mg/kg/day of prednisone equivalent.
• PROCUREMENT: Severe previous toxicity from cyclophosphamide or fludarabine based on the enrolling physician’s assessment.
• PROCUREMENT: Human immunodeficiency virus (HIV) infection.
• PROCUREMENT: History of hypersensitivity, anaphylaxis, and/or adverse event with etanercept.
• TREATMENT: Rapidly progressive disease.
• TREATMENT: Currently receiving any investigational drugs.
• TREATMENT: History or hypersensitivity to murine protein-containing products.
• TREATMENT: Cardiomegaly or bilateral pulmonary infiltrates on chest radiograph or CT. However, patients with cardiomegaly on imaging may be enrolled if they have an assessment of cardiac function (i.e., echocardiography [ECHO] or multigated acquisition scan [MUGA]) within 3 weeks of starting protocol therapy that is within normal limits. Additionally, patients with bilateral pulmonary infiltrates on imaging may be enrolled if the lesions are not consistent with active neuroblastoma (i.e., negative on functional imaging with positron emission tomography [PET] or MIBG, or by pathologic assessment).
• TREATMENT: Tumor potentially causing airway obstruction.
• TREATMENT: Pregnancy or lactation or not willing to use birth control.
• TREATMENT: Currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine. * Patients may receive treatment if treated with corticosteroids with dose of less than 0.5 mg/kg/day of prednisone equivalent.
• TREATMENT: Severe previous toxicity form cyclophosphamide or fludarabine based on the enrolling physician’s assessment.
• TREATMENT: HIV infection.
• TREATMENT: History of hypersensitivity, anaphylaxis, and/or adverse event with etanercept.