TY - JOUR
T1 - Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation
T2 - A Pediatric Blood and Marrow Transplant Consortium Trial
AU - Morris, Joan
AU - Rudebeck, Mattias
AU - Neudorf, Steven
AU - Moore, Theodore
AU - Duerst, Reggie
AU - Shah, Ami J.
AU - Graham, Michael
AU - Aquino, Victor
AU - Morris, Christopher
AU - Olsson, Birgitta
N1 - Publisher Copyright:
© 2016 American Society for Blood and Marrow Transplantation.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16 years) and 3 dose levels (40, 60, and 80 μg/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-μg/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen.
AB - Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16 years) and 3 dose levels (40, 60, and 80 μg/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-μg/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen.
KW - Keratinocyte growth factor
KW - Palifermin
KW - Pediatric
KW - Pharmacokinetics
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=84963642074&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84963642074&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2016.02.016
DO - 10.1016/j.bbmt.2016.02.016
M3 - Article
C2 - 26968792
AN - SCOPUS:84963642074
SN - 1083-8791
VL - 22
SP - 1247
EP - 1256
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 7
ER -