Anti-GD2 4th Generation CART Cells Targeting Refractory and/or Recurrent Neuroblastoma

Prior treatment

• Untreated central nervous system (CNS) metastasis:
  • Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
• Previous treatment with other genetically engineered GD2-CAR T cells.
• Patients who require systemic corticosteroid or other immunosuppressive therapy.
• Patients previously experienced severe toxicity from cyclophosphamide or fludarabine.

Other illness

• Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, with the exception of grade 3 hematologic toxicity.
• Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.

Other

• Evidence of tumor potentially causing airway obstruction.
• Inability to comply with protocol requirements.
• Insufficient CAR T cells availability.

• Patients with neuroblastoma have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive/persistent or recurrent.
• The GD2 antigen status of the neuroblastoma will be determined for eligibility. Positive expression is defined by GD2 antibody staining results based on immunohistochemistry or flow cytometry analyses.
• Body weight greater than or equal to 10 kg.
• Age: ≥1 year and ≤ 14 years of age at the time of enrollment.
• Life expectancy: at least 8 weeks.
• Prior Therapy: 1) There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less. 2) Must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection. 3) At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic nonmyelosuppressive regimen. 4) At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody. 5) At least 1 weeks since any radiation therapy at the time of study entry.
• Karnofsky/jansky score of 60% or greater.
• Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent .
• Pulse Ox greater than or equal to 90% on room air.
• Liver function: defined as alanine transaminase (ALT) \<3x upper limit of normal (ULN), aspartate aminotransferase (AST) \<3x ULN; serum bilirubin and alkaline phosphatase \<2x ULN.
• Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
• Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
• Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease not evaluable for hematologic toxicity.
• Patients must have autologous transduced T cells at levels greater than or equal to 2x10e5 cells per kilogram body weight.
• For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.