A feasibility and phase II study of the hu14.18-IL2 immunocytokine in combination with GM-CSF and isotretinoin in patients with recurrent or refractory neuroblastoma: A Children’s Oncology Group study.

10017 Background: Combining anti-GD2 (disialoganglioside) monoclonal antibody with GM-CSF, IL2 and isotretinoin is now standard of care for high-risk neuroblastoma (NB) minimal residual disease (MRD) therapy. The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in NB and is more effective in NB-bearing mice than antibody and cytokine given separately. We therefore evaluated the safety, tolerability and anti-tumor activity of hu14.18-IL2 given with GM-CSF and isotretinoin in a schedule similar to current MRD therapy. Methods: Hu14.18-IL2 was given at the phase II dose (12 mg/m2) on days 4-6 of a 28 day cycle with GM-CSF (250 μg/m2/dose, days 1-2, 8-14) and isotretinoin (160 mg/m2/day, days 11-25). Tolerability was determined based on the number of patients who developed an unacceptable toxicity (required pressor support or intubation). Response was evaluated every 2 cycles for patients with disease measurable by standard radiologic criteria (stratum 1), and for patients wit...