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Safety and Efficacy of Gemtuzumab Ozogamicin in Combination With Chemotherapy for Pediatric Acute Myeloid Leukemia: A Report From The Children's Oncology Group

Richard Aplenc, Todd A. Alonzo, Robert B. Gerbing, Beverly J. Lange, Craig A. Hurwitz, Robert J. Wells, Irwin Bernstein, Patrick Buckley, Kathleen Krimmel, Franklin O. Smith, Eric L. Sievers, Robert J. Arceci

From the University of Pennsylvania, Philadelphia, PA; University of Southern California, Los Angeles; Children's Oncology Group, Arcadia, CA; Maine Children's Cancer Program and Barbara Bush Children's Hospital at Maine Medical Center, Scarborough, ME; M.D. Anderson Cancer Center, Houston, TX; Children's Hospital and Regional Medical Center; Fred Hutchinson Cancer Research Center and University of Washington, Department of Pediatrics; Seattle Genetics, Seattle, WA; Duke University Medical Center, Durham, NC; Rainbow Babies and Children's Hospital, Cleveland; University of Cincinnati, Cincinnati, OH; and Johns Hopkins University, Baltimore, MD

Corresponding author: Richard Aplenc, MD, Children's Hospital of Philadelphia, Center for Clinical Epidemiology/Biostatistic, 3615 Civic Center Blvd, 916G ARC, Philadelphia, PA 19104-4318; e-mail: raplenc{at}mail.med.upenn.edu

Purpose: While gemtuzumab ozogamicin (GTMZ) is commonly used in the treatment of acute myeloid leukemia (AML) in combination with standard chemotherapy agents, the pediatric maximum-tolerated dose (MTD) of GMTZ in combination with chemotherapy has not been determined.

Patients and Methods: The Children's Oncology Group AAML00P2 trial sought to define the MTD of GMTZ in combination with cytarabine and mitoxantrone and cytarabine and l-asparaginase chemotherapy regimens.

Results: The MTD for GMTZ in combination with cytarabine and mitoxantrone was 3 mg/m² while the MTD in combination with cytarabine and l-asparaginase was 2 mg/m². Toxicities observed in both treatment regimens were typical of those seen in the relapsed AML setting and consisted primarily of infectious complications. The overall remission response rate (mean ± SE) was 45% ± 15% and the 1 year event-free survival and overall survival estimates were 38% ± 14% and 53% ± 15%, respectively.

Conclusion: This trial determined the pediatric MTD for GMTZ with two commonly used AML chemotherapy combinations. Based on these results, an ongoing phase III trial conducted within the Children's Oncology Group is evaluating the effect of GMTZ when added to standard AML therapy.

Supported by Grants No. 1 R01 CA108862 (R.A.) and 1 U10 CA98413-01 (T.A.A.). A complete listing of grant support for research conducted by Children's Cancer Group and Pediatric Oncology Group before initiation of the Children's Oncology Group grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.