title: A Phase 2 Trial of Fludarabine Combined With Subcutaneous Alemtuzumab for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia.
abstract: BACKGROUND
  Alemtuzumab is effective in fludarabine-refractory patients with chronic lymphocytic leukemia. We performed a phase 2 study of alemtuzumab in combination with fludarabine in patients with relapsed disease.
  
  
  METHODS
  Patients received alemtuzumab and fludarabine daily on days 1 to 5 of a 28-day cycle for up to 6 cycles with the primary objective of determining the rate of complete response. Of 60 enrolled patients, 51 had previously received fludarabine, and 60% had received 3 or more prior therapies.
  
  
  RESULTS
  Five patients experienced complete response (8.3%) and 12 experienced partial response, yielding an overall response rate of 28.3% for the intention-to-treat population. Among the 41 patients who completed at least 4 cycles of therapy, the complete response rate was 20%. Median progression-free survival was 211 days. Forty-seven percent of patients experienced cytomegalovirus viremia, including 4 patients with symptomatic cytomegalovirus disease. All patients responded to antiviral therapy.
  
  
  CONCLUSIONS
  Despite some evidence of efficacy in this setting, the primary end point for the study was not met. In the era of targeted agents that are well tolerated, the combination of fludarabine and alemtuzumab should be used rarely for a select group of fit patients who are refractory to standard therapies.
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: crflowe@emory.edu.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Flowers
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Hilary
authors.initials: H
authors.lastname: Rosenthal
authors.affiliation: University of Chicago Medical Center and Hospitals, Chicago, IL.
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.affiliation: Oncology-Hematology Associates, PA, Clinton, MD.
authors.forename: Harvey I
authors.initials: HI
authors.lastname: Katzen
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Jonathon B
authors.initials: JB
authors.lastname: Cohen
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Rajni
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Birmingham Hematology and Oncology Associates, LLC, Birmingham, AL.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Lakhanpal
authors.affiliation: Oregon Health & Science University, Portland, OR.
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA.
authors.forename: David L
authors.initials: DL
authors.lastname: Jaye
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019233:Retreatment; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine
keywords: Alemtuzumab; Chronic lymphocytic leukemia; Fludarabine; Minimal residual disease; Small lymphocytic lymphoma