Phase I Study of ch14.18 With Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-2 in Children With Neuroblastoma After Autologous Bone Marrow Transplantation or Stem-Cell Rescue: A Report From the Children's Oncology Group

Purpose Recurrence of high-risk neuroblastoma is common despite multimodality therapy. ch14.18, a chimeric human/murine anti-GD2 antibody, lyses neuroblastoma cells. This study determined the maximum tolerable dose (MTD) and toxicity of ch14.18 given in combination with interleukin-2 (IL-2) after high-dose chemotherapy (HDC)/stem-cell rescue (SCR). Biologic correlates including ch14.18 levels, soluble IL-2 receptor levels, and human antichimeric antibody (HACA) activity were evaluated. Patients and Methods Patients were given ch14.18 for 4 days at 28-day intervals. Patients received IL-2 during the second and fourth courses of ch14.18 and granulocyte-macrophage colony-stimulating factor (GM-CSF) during the first, third, and fifth courses. The MTD was determined based on toxicities occurring with the second course. After the determination of the MTD, additional patients were treated to confirm the MTD and to clarify appropriate supportive care. Results Twenty-five patients were enrolled. The MTD of ch14.18...