title: Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108.
abstract: OBJECTIVE
  Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL).
  
  
  METHODS
  Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles.
  
  
  RESULTS
  Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response.
  
  
  CONCLUSIONS
  Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL.
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI. paul_barr@urmc.rochester.edu.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Barr
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Catherine
authors.initials: C
authors.lastname: Spier
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Daruka
authors.initials: D
authors.lastname: Mahadevan
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Michael
authors.initials: M
authors.lastname: LeBlanc
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Ul Haq
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Huber
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Nina D
authors.initials: ND
authors.lastname: Wagner-Johnston
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Horwitz
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Fisher
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Brad S
authors.initials: BS
authors.lastname: Kahl
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Bartlett
authors.affiliation: Paul M. Barr and Jonathan W. Friedberg, University of Rochester, Rochester; Steven M. Horwitz, Memorial Sloan Kettering Cancer Center, New York, NY; Hongli Li and Michael LeBlanc, SWOG Statistical Office, Seattle, WA; Catherine Spier, University of Arizona College of Medicine, Tucson, AZ; Daruka Mahadevan, Mansoor Ul Haq, and Bryan D. Huber, University of Tennessee Health Sciences Center, Memphis, TN; Christopher R. Flowers, Emory University, Atlanta, GA; Nina D. Wagner-Johnston and Nancy L. Bartlett, Washington University School of Medicine, St. Louis, MO; Richard I. Fisher, Temple University, Philadelphia, PA; Bruce D. Cheson, Georgetown University Hospital, Washington, DC; Sonali M. Smith, The University of Chicago, Chicago, IL; and Brad S. Kahl, University of Wisconsin, Madison, WI.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Friedberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001381:Azepines / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy* / Q000473:pathology; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; D014408:Biomarkers, Tumor; D016207:Cytokines; C550258:MLN 8237; D011743:Pyrimidines