title: Multicenter phase II trial of enzastaurin in patients with relapsed or refractory advanced cutaneous T-cell lymphoma.
abstract: This multicenter, single-arm, open-label non-randomized phase II trial (NCT00744991) was conducted in patients with recurrent/refractory mycosis fungoides (MF), stage IB-IVB, or Sézary syndrome (SS). A Simon two-stage design required 25 patients enrolled in stage 1 with ≥7 confirmed objective responses for expansion into stage 2. Patients were treated with oral enzastaurin (250 mg twice daily) until disease progression or intolerable toxicity. The primary endpoint was investigator-assessed response rate; secondary endpoints were time to objective response, response duration, time-to-progression, patient-reported pruritus, and safety/tolerability. Twenty-five patients were enrolled. A partial response was observed in one patient with MF. Median time-to-progression was 78 and 44 days in MF and SS, respectively. Self-reported pruritus relief and improved composite pruritus-specific symptom scores were documented in six and four patients, respectively. Enzastaurin was well tolerated with mostly grade 1-2 adverse events, mainly diarrhea and fatigue. There were two adverse event-related drug discontinuations with one possibly treatment-related.
authors.affiliation: Department of Dermatology, Northwestern University, Chicago, IL 60611, USA. c-querfeld@northwestern.edu
authors.forename: Christiane
authors.initials: C
authors.lastname: Querfeld
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Kuzel
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Amy
authors.initials: A
authors.lastname: Musiek
authors.forename: Alain H
authors.initials: AH
authors.lastname: Rook
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Mark
authors.forename: Lauren
authors.initials: L
authors.lastname: Pinter-Brown
authors.forename: Oday
authors.initials: O
authors.lastname: Hamid
authors.forename: Boris
authors.initials: B
authors.lastname: Lin
authors.forename: Ying
authors.initials: Y
authors.lastname: Bian
authors.forename: Mark
authors.initials: M
authors.lastname: Boye
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Day
authors.forename: Steven T
authors.initials: ST
authors.lastname: Rosen
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003967:Diarrhea / Q000139:chemically induced; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D012008:Recurrence; D012751:Sezary Syndrome / Q000188:drug therapy / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D007211:Indoles; C504878:enzastaurin