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This Phase 1 gene transfer study tests T cells carrying a chimeric antigen receptor (CAR) that recognizes GD2, a protein found on almost all neuroblastoma cells, in participants with relapsed or refractory neuroblastoma. Because an earlier trial showed GD2-CAR T cell infusions were safe and that time to progression was longer when the cells persisted in the blood for more than 6 weeks, this study adds new genes to help the cells last longer, including an iCaspase suicide safety switch; cyclophosphamide (Cytoxan), fludarabine (Fludara) and pembrolizumab (Keytruda) are also used. Eligibility requires high-risk neuroblastoma with persistent or relapsed disease, a life expectancy of at least 12 weeks, a Karnofsky/Lansky score of 60% or greater, and informed consent.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria: PROCUREMENT * High risk neuroblastoma with persistent or relapsed disease * Life expectancy of at least 12 weeks * Karnofsky/Lansky score of 60% or greater * Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies) * Informed consent and assent (as applicable) obtained from parent/guardian and child TREATMENT: * High risk neuroblastoma with persistent or relapsed disease * Life expectancy of at least 12 weeks * Karnofsky/Lansky score of 60% or greater * Patients must have an ANC greater than or equal to 500, platelet count greater than or equal to 20,000 * Pulse Ox greater than or equal to 90% on room air * AST and ALT less than 5 times the upper limit of normal * Total bilirubin less than 3 times the upper limit of normal * Serum creatinine less than 3 times upper limit of normal. Creatinine clearance is needed for patients with creatinine greater than 1.5 times upper limit of normal * TSH normal for age. Patients using thyroid medication to facilitate a euthyroid state must be on a stable dose for at least 1 month prior to planned infusion * Recovered from acute effects of all prior chemotherapy. If some effects of therapy have become chronic (i.e., treatment associated thrombocytopenia), the patient must be clinically stable and meet all other eligibility criteria * Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies * Patients must have autologous transduced activated T-cells with greater than or equal to 20% expression of GD2 * Pembrolizumab available for infusion * Informed consent and assent (as applicable) obtained from parent/guardian and child Exclusion Criteria: PROCUREMENT: * Rapidly progressive disease * History of hypersensitivity to murine protein containing products TREATMENT: * Rapidly progressive disease * Currently receiving other investigational drugs * History of hypersensitivity to murine protein containing products * History of 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., ECHO or 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 PET or MIBG, or by pathologic assessment). * Evidence of tumor potentially causing airway obstruction * Patients who are pregnant, lactating, or unwilling to use birth control * Patients currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine * Patients previously experienced severe toxicity from cyclophosphamide or fludarabine * Severe previous toxicity from pembrolizumab or other PD-1 targeted antibody