title: A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML).
abstract: To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML).
  
  
  
  Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) <0.25 × 10(3) cells/dL and a platelet count <35 × 10(3) cells/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations.
  
  
  
  Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose-limiting toxicities for ruxolitinib were identified. One subject had grade (G)3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28-409 days). Four had hematologic improvement and one patient had a partial response per 2006 International Working Group (IWG) criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease-related symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (n = 7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF-dependent STAT5 phosphorylation.
  
  
  
  The recommended phase II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study. Clin Cancer Res; 22(15); 3746-54. ©2016 AACRSee related commentary by Solary, p. 3707.
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. eric.padron@moffitt.org.
authors: Eric
authors: E
authors: Padron
authors: Department of Oncology, Sidney Kimmel Cancer Center, Baltimore, Maryland.
authors: Amy
authors: A
authors: Dezern
authors: Translational Research Unit, IIS-A, CIBER de Enfermedades Raras, CIBERER, Zaragoza, Spain.
authors: Marcio
authors: M
authors: Andrade-Campos
authors: Incyte Corporation, Wilmington, Delaware.
authors: Kris
authors: K
authors: Vaddi
authors: Incyte Corporation, Wilmington, Delaware.
authors: Peggy
authors: P
authors: Scherle
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Qing
authors: Q
authors: Zhang
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Yan
authors: Y
authors: Ma
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Maria E
authors: ME
authors: Balasis
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Sara
authors: S
authors: Tinsley
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Hanadi
authors: H
authors: Ramadan
authors: Leukemia Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors: Cassandra
authors: C
authors: Zimmerman
authors: Adult Leukemia Program, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors: David P
authors: DP
authors: Steensma
authors: Leukemia Program, Weill Medical College of Cornell University, New York, New York.
authors: Gail J
authors: GJ
authors: Roboz
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Jeffrey E
authors: JE
authors: Lancet
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Alan F
authors: AF
authors: List
authors: Leukemia Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors: Mikkael A
authors: MA
authors: Sekeres
authors: Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Rami S
authors: RS
authors: Komrokji
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D008297:Male; 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; D050799:STAT5 Transcription Factor / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D050799:STAT5 Transcription Factor; C540383:ruxolitinib; D016178:Granulocyte-Macrophage Colony-Stimulating Factor