Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group.
OBJECTIVE
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.


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/m(2) while the MTD in combination with cytarabine and l-asparaginase was 2 mg/m(2). 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.


CONCLUSIONS
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.
Aplenc
Richard
R
Children's Hospital of Philadelphia, Center for Clinical Epidemiology/Biostatistic, 3615 Civic Center Blvd, 916G ARC, Philadelphia, PA 19104-4318, USA. raplenc@mail.med.upenn.edu
Alonzo
Todd A
TA
Gerbing
Robert B
RB
Lange
Beverly J
BJ
Hurwitz
Craig A
CA
Wells
Robert J
RJ
Bernstein
Irwin
I
Buckley
Patrick
P
Krimmel
Kathleen
K
Smith
Franklin O
FO
Sievers
Eric L
EL
Arceci
Robert J
RJ
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate
D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D000079982:Gemtuzumab; D008942:Mitoxantrone; D001215:Asparaginase