title: A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia.
abstract: This Phase I study of clofarabine with etoposide and cyclophosphamide for children with relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities and the recommended phase 2 doses (RP2Ds). All three drugs were administered for five consecutive days in induction and four consecutive days in consolidation, for a maximum of eight cycles. A total of 25 patients (20 ALL and 5 AML) were enrolled in five cohorts. An MTD was not reached. The RP2Ds of clofarabine, cyclophosphamide and etoposide were 40, 440 and 100 mg/m(2)/day, respectively. Complete remission (CR) was achieved in 10 patients (ALL: nine; AML: one), and CR without platelet recovery in six patients (ALL: two; AML: four) for an overall response rate of 64% (ALL: 55%; AML: 100%). Of the 16 responders, 9 patients proceeded to hematopoietic stem cell transplantation. In conclusion, the combination of clofarabine, etoposide and cyclophosphamide was well tolerated and effective in pediatric patients with relapsed/refractory leukemia. Of note, the phase II portion of the trial was amended after the occurrence of unexpected hepatotoxicity. The ongoing phase II study will evaluate the efficacy and safety of this regimen in ALL patients.
authors.affiliation: Department of Pediatric Hematology-Oncology, Children's Memorial Hospital/Northwestern University Feinberg School of Medicine, 2300 Children's Plaza, Chicago, IL 60614-3394, USA. nhijiya@childrensmemorial.org
authors.forename: N
authors.initials: N
authors.lastname: Hijiya
authors.forename: P
authors.initials: P
authors.lastname: Gaynon
authors.forename: E
authors.initials: E
authors.lastname: Barry
authors.forename: L
authors.initials: L
authors.lastname: Silverman
authors.forename: B
authors.initials: B
authors.lastname: Thomson
authors.forename: R
authors.initials: R
authors.lastname: Chu
authors.forename: T
authors.initials: T
authors.lastname: Cooper
authors.forename: R
authors.initials: R
authors.lastname: Kadota
authors.forename: M
authors.initials: M
authors.lastname: Rytting
authors.forename: P
authors.initials: P
authors.lastname: Steinherz
authors.forename: V
authors.initials: V
authors.lastname: Shen
authors.forename: S
authors.initials: S
authors.lastname: Jeha
authors.forename: R
authors.initials: R
authors.lastname: Abichandani
authors.forename: W L
authors.initials: WL
authors.lastname: Carroll
mesh_terms: D000208:Acute Disease; D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use / Q000633:toxicity; D001087:Arabinonucleosides / Q000008:administration & dosage*; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D000077866:Clofarabine; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005047:Etoposide / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000150:complications / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy; D020714:Maximum Tolerated Dose; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy; D012074:Remission Induction; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D005047:Etoposide; D000077866:Clofarabine; D003520:Cyclophosphamide