Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia.

Abstract

This open-label, dose-escalation study evaluated the safety and efficacy of single-agent gemtuzumab ozogamicin, a humanized anti-CD33 antibody-targeted chemotherapeutic agent, for pediatric patients with multiple relapsed or primary refractory acute myeloid leukemia (AML). Twenty-nine children 1 to 16 years of age (relapsed disease, 19; refractory disease, 10) received gemtuzumab ozogamicin ranging from 6 to 9 mg/m2 per dose for 2 doses (separated by 2 weeks) infused over 2 hours. All patients had anticipated myelosuppression. Other toxicities included grade 3/4 hyperbilirubinemia (7%) and elevated hepatic transaminase levels (21%); the incidence of grade 3/4 mucositis (3%) or sepsis (24%) was relatively low. One patient treated at 9 mg/m2 developed veno-occlusive disease (VOD) of the liver and defined the dose-limiting toxicity. Thirteen patients underwent hematopoietic stem-cell transplantation less than 3.5 months after the last dose of gemtuzumab ozogamicin; 6 (40%) developed VOD. Eight of 29 (28%) patients achieved overall remission. Remissions were comparable in patients with refractory (30%) and relapsed (26%) disease. Mean multidrug resistance-protein-mediated drug efflux was significantly lower in the leukemic blasts of patients achieving remission (P < .005). Gemtuzumab ozogamicin was relatively well tolerated at 6 mg/m2 for 2 doses and was equally effective in patients with refractory and relapsed disease. Further studies in combination with standard induction therapy for childhood AML are warranted.

• Authors: Robert J Arceci, Jane Sande, Beverly Lange, Kevin Shannon, Janet Franklin, Raymond Hutchinson, Terry A Vik, David Flowers, Richard Aplenc, Mark S Berger, Matthew L Sherman, Franklin O Smith, Irwin Bernstein, Eric L Sievers
• Journal: Blood (Blood) Vol. 106 Issue 4 Pg. 1183-8 (Aug 15 2005) ISSN: 0006-4971 [Print] United States
• PMID: 15886328 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoglycosides
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD33 protein, human
• Sialic Acid Binding Ig-like Lectin 3
• Gemtuzumab

Topics

• Acute Disease
• Adolescent
• Aminoglycosides (administration & dosage, toxicity)
• Antibodies, Monoclonal (administration & dosage, toxicity)
• Antibodies, Monoclonal, Humanized
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• Blast Crisis
• Child
• Child, Preschool
• Drug Resistance
• Female
• Gemtuzumab
• Hematopoietic Stem Cell Transplantation
• Hepatic Veno-Occlusive Disease (chemically induced)
• Humans
• Hyperbilirubinemia (chemically induced)
• Infant
• Leukemia, Myeloid (complications, drug therapy, therapy)
• Male
• Maximum Tolerated Dose
• Remission Induction (methods)
• Salvage Therapy (methods)
• Sialic Acid Binding Ig-like Lectin 3