1. Phase I study of chimeric human/murine anti-ganglioside G(D2) monoclonal antibody (ch14.18) with granulocyte-macrophage colony-stimulating factor in children with neuroblastoma immediately after hematopoietic stem-cell transplantation: a Children's Cancer Group Study.
- Author
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Ozkaynak MF, Sondel PM, Krailo MD, Gan J, Javorsky B, Reisfeld RA, Matthay KK, Reaman GH, and Seeger RC
- Subjects
- Adolescent, Animals, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal blood, Antibodies, Monoclonal immunology, Antibody Formation immunology, Antibody-Dependent Cell Cytotoxicity, Child, Child, Preschool, Combined Modality Therapy, Disease Progression, Dose-Response Relationship, Immunologic, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Mice, Neuroblastoma immunology, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins adverse effects, Recombinant Fusion Proteins immunology, Antibodies, Monoclonal adverse effects, Gangliosides immunology, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Hematopoietic Stem Cell Transplantation, Neuroblastoma therapy
- Abstract
Purpose: Ganglioside G(D2) is strongly expressed on the surface of human neuroblastoma cells. It has been shown that the chimeric human/murine anti-G(D2) 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 maximum-tolerated 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/microL after HSCT. ch14.18 was infused intravenously over 5 hours daily for 4 consecutive days. Patients received GM-CSF 250 microg/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 GM-CSF 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.
- Published
- 2000
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