Phase I S tudy o f C himeric H uman/Murine Anti-Ganglioside G D2 Monoclonal A ntibody ( ch14.18) W ith Granulocyte-Macr ophage C olony-Stimulati ng F actor i n Children W ith N euroblastoma I mmediately A fter Hematopoietic S tem-Cell T ransplantation: A C hildren's Cancer G roup S tudy

Purpose: Ganglioside GD2 is strongly expressed on the surface of human neuroblastoma cells. It has been shown that the chimeric human/murine anti-GD2 monoclonal antibody (ch14.18) can induce lysis of neuroblastoma cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. The purposes of the study were (1) to determine the maximumtolerated dose (MTD) of ch14.18 in combination with standard dose granulocyte-macrophage colony-stimulating factor (GM-CSF) for patients with neuroblastoma who recently completed hematopoietic stem-cell transplantation (HSCT), and (2) to determine the toxicities of ch14.18 with GM-CSF in this setting. Patients and Methods: Patients became eligible when the total absolute phagocyte count (APC) was greater than 1,000/mL after HSCT. ch14.18 was infused intravenously over 5 hours daily for 4 consecutive days. Patients received GM-CSF 250 mg/m 2 /d starting at least 3 days before ch14.18 and continued for 3 days after the completion of ch14.18. The ch14.18 dose levels were 20, 30, 40, and 50 mg/m 2 /d. In the absence of progressive disease, patients were allowed to receive up to six 4-day courses of ch14.18 therapy with GM-CSF. Nineteen patients with neuroblastoma were treated. Results: A total of 79 courses were administered. No toxic deaths occurred. The main toxicities were severe neuropathic pain, fever, nausea/vomiting, urticaria, hypotension, mild to moderate capillary leak syndrome, and neurotoxicity. Three dose-limiting toxicities were observed among six patients at 50 mg/m 2 /d: intractable neuropathic pain, grade 3 recurrent urticaria, and grade 4 vomiting. Human antichimeric antibody developed in 28% of patients. Conclusion: ch14.18 can be administered with GMCSF after HSCT in patients with neuroblastoma with manageable toxicities. The MTD is 40 mg/m 2 /d for 4 days when given in this schedule with GM-CSF. J Clin Oncol 18:4077-4085. © 2000 by American Society of Clinical Oncology.