title: A phase I/II study of the Janus kinase (JAK)1 and 2 inhibitor ruxolitinib in patients with relapsed or refractory acute myeloid leukemia.
abstract: BACKGROUND
  Ruxolitinib is a potent and specific JAK1/JAK2 inhibitor recently approved for the treatment of myelofibrosis.
  
  
  METHODS
  We conducted a single-center phase I/II clinical study testing 3 dose levels (50 mg b.i.d. [n = 4], 100 mg b.i.d. [n = 5], and 200 mg b.i.d. [n = 18]). We enrolled 27 patients older than 14 years with relapsed or refractory acute myeloid leukemia (n = 26) or acute lymphoid leukemia (n = 1).
  
  
  RESULTS
  The median age was 66 (range, 25-88) years. Thirteen patients were evaluable for dose-limiting toxicities. The most common Grade 3 or 4 nonhematologic event was infection (n = 26 events; most frequently pneumonia; 15 of 26; 58%). One patient with multiple relapses after 7 lines of therapy had a CRp at a ruxolitinib dose of 200 mg b.i.d.
  
  
  CONCLUSIONS
  In this cohort of heavily pretreated patients with relapsed or refractory acute leukemias, ruxolitinib was overall reasonably well tolerated, with 1 patient achieving CRp.
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Tapan
authors.initials: T
authors.lastname: Kadia
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Kate
authors.initials: K
authors.lastname: Newberry
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Sara
authors.initials: S
authors.lastname: Dellasala
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX. Electronic address: sverstov@mdanderson.org.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009570:Nitriles; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: Acute myelogenous leukemia; Clinical study; JAK2V617 mutation; Janus kinase inhibitor; Myelofibrosis; Ruxolitinib