Therapy for Children With Advanced Stage Neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in childhood, with nearly 50% of patients presenting with widespread metastatic disease. The current treatment for this group of high-risk patients includes intensive multi-agent chemotherapy (induction) followed by myeloablative therapy with stem-cell rescue (consolidation) and then treatment of minimal residual disease (MRD) with isotretinoin. Recently a new standard of care was established by enhancing the treatment of MRD with the addition of a monoclonal antibody (ch14.18) which targets a tumor-associated antigen, the disialoganglioside GD2, which is uniformly expressed by neuroblasts. Despite improvement in 2-year event-free survival (EFS) of 20%, more than one-third of children with high-risk neuroblastoma (HR defined in) still cannot be cured by this approach. Therefore, novel therapeutic approaches are needed for this subset of patients. This study will be a pilot Phase II study of a unique anti-disialoganglioside (anti-GD2) monoclonal antibody (mAb) called hu14.18K322A, given with induction chemotherapy. PRIMARY OBJECTIVE: * To study the efficacy [response: complete remission + partial remission (CR+PR)] to two initial courses of cyclophosphamide and topotecan combined with hu14.18K322A (4 doses/course followed by GM-CSF) in previously untreated children with high-risk neuroblastoma. * To estimate the event-free survival of patients with newly diagnosed high-risk neuroblastoma treated with the addition of hu14.18K322A to treatment. SECONDARY OBJECTIVES: * To study the feasibility of delivering hu14.18K322A to 6 cycles induction chemotherapy and describe the antitumor activity (CR+PR) of this 6 course induction therapy. * To estimate local control and pattern of failure associated with focal intensity modulated or proton beam radiation therapy dose delivery in high-risk abdominal neuroblastoma. * To describe the tolerability of four doses of hu14.18K322A with allogeneic natural killer (NK) cells from an acceptable parent, in the immediate post-transplant period [day +2 - +5 after peripheral blood stem cell (PBSC) infusion] in consenting participants. * To describe the tolerability of hu14.18K322A with interleukin-2 and GM-CSF as treatment for minimal residual disease (MRD).