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.
J Clin Oncol
; 18(24): 4077-85, 2000 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-11118469
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 ANDMETHODS:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator Estimulador de Colônias de Granulócitos e Macrófagos
/
Transplante de Células-Tronco Hematopoéticas
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Gangliosídeos
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Anticorpos Monoclonais
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Neuroblastoma
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Animals
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
J Clin Oncol
Ano de publicação:
2000
Tipo de documento:
Article