title: Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia.
abstract: We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Eghtedar
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Carol
authors.initials: C
authors.lastname: Bivins
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Solly
authors.initials: S
authors.lastname: George
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Scherle
authors.forename: Robert C
authors.initials: RC
authors.lastname: Newton
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000473:pathology; D009570:Nitriles; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D012008:Recurrence; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D053612:Janus Kinases