title: Phase I/II study of idarubicin given with continuous infusion fludarabine followed by continuous infusion cytarabine in children with acute leukemia: a report from the Children's Cancer Group.
abstract: OBJECTIVE
  The Children's Cancer Group (CCG) undertook a phase I study (CCG-0922) to determine a tolerable dose of idarubicin given with fludarabine and cytarabine in children with relapsed or refractory leukemia. The phase I study was extended to a limited phase II study to assess the activity of this combination in children with acute myelogenous leukemia (AML).
  
  
  METHODS
  This was a multiinstitutional study within the CCG. Eleven patients were entered onto the phase I study: seven with AML, three with acute lymphoblastic leukemia (ALL), and one with chronic myelogenous leukemia (CML). The maximal-tolerated dose (MTD) of fludarabine and cytarabine determined in a previous study was a fludarabine loading dose (LD) of 10.5 mg/m2 followed by a continuous infusion (CI) of 30.5 mg/m2/24 hours for 48 hours, followed by cytarabine LD 390 mg/m2, then CI 101 mg/m2/h for 72 hours. Idarubicin was given at three dose levels: 6, 9, and 12 mg/m2 intravenously (I.V.) on days 0, 1, and 2. The phase II portion of the trial included 10 additional patients with relapsed or refractory AML.
  
  
  RESULTS
  A dose of idarubicin 12 mg/m2/d for 3 days given in combination with fludarabine and cytarabine was tolerated. The major toxicity encountered was hematologic. Nonhematologic toxicities included transaminase elevations, hyperbilirubinemia, and infections. Eight of 10 patients with AML in the phase II portion (12 mg/m2 idarubicin) achieved a complete remission (CR).
  
  
  CONCLUSIONS
  This combination is active in patients with relapsed or refractory AML. The major toxicity encountered is hematologic. This regimen may be useful therapy for AML and should be compared with standard induction therapy in children with newly diagnosed AML.
authors.affiliation: Children's National Medical Center, Washington, DC, USA. pdinndor@cnmc.org
authors.forename: P A
authors.initials: PA
authors.lastname: Dinndorf
authors.forename: V I
authors.initials: VI
authors.lastname: Avramis
authors.forename: S
authors.initials: S
authors.lastname: Wiersma
authors.forename: M D
authors.initials: MD
authors.lastname: Krailo
authors.forename: W
authors.initials: W
authors.lastname: Liu-Mares
authors.forename: N L
authors.initials: NL
authors.lastname: Seibel
authors.forename: J K
authors.initials: JK
authors.lastname: Sato
authors.forename: R B
authors.initials: RB
authors.lastname: Mosher
authors.forename: J F
authors.initials: JF
authors.lastname: Kelleher
authors.forename: G H
authors.initials: GH
authors.lastname: Reaman
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D007262:Infusions, Intravenous; D007938:Leukemia / Q000188:drug therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine; D015255:Idarubicin