title: Final results of EFC6663: a multicenter, international, phase 2 study of alvocidib for patients with fludarabine-refractory chronic lymphocytic leukemia.
abstract: Early phase studies of alvocidib showed activity in relapsed CLL including patients with high risk genomic features and those refractory to fludarabine. A multi-center, international, phase II study of alvocidib in fludarabine refractory CLL was undertaken to validate these early results. Patients with fludarabine refractory CLL or prolymphocytic leukemia arising from CLL were treated with single agent alvocidib. The primary outcome measure was overall response rate, with secondary outcomes including survival, toxicity, and response duration. One hundred and sixty five patients were enrolled and 159 patients were treated. The median age was 61 years, the median number of prior therapies was 4, and 96% of patients were fludarabine refractory. The investigator-assessed overall response rate was 25%; the majority of responses were partial. Response rates were lower among patients with del(17p) (14%), but equivalent in patients with del(11q) or bulky lymphadenopathy. Median progression free and overall survival were 7.6 and 14.6 months, respectively. Tumor lysis occurred in 39 patients (25%), and 13 received hemodialysis. Diarrhea, fatigue, and hematologic toxicities were common. Alvocidib has clinical activity in patients with advanced, fludarabine refractory CLL. Future studies should focus on discovery of biomarkers of clinical response and tumor lysis, and enhanced supportive care measures.
authors: Duke University Medical Center, Durham, NC, United States.
authors: Mark C
authors: MC
authors: Lanasa
authors: The Ohio State University, Columbus, OH, United States.
authors: Leslie
authors: L
authors: Andritsos
authors: Dana-Farber/Harvard Cancer Center, Boston, MA, United States.
authors: Jennifer R
authors: JR
authors: Brown
authors: Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Janice
authors: J
authors: Gabrilove
authors: Department of Onco-Hematology and Division of Molecular Oncology, Istituto Scientifico San Raffaele and Università, Vita-Salute San Raffaele, Milan, Italy.
authors: Federico
authors: F
authors: Caligaris-Cappio
authors: Department of Onco-Hematology and Division of Molecular Oncology, Istituto Scientifico San Raffaele and Università, Vita-Salute San Raffaele, Milan, Italy.
authors: Paolo
authors: P
authors: Ghia
authors: University of Chicago, Chicago, IL, United States.
authors: Richard A
authors: RA
authors: Larson
authors: Moores UCSD Cancer Center, San Diego, CA, United States.
authors: Thomas J
authors: TJ
authors: Kipps
authors: Hôpital pitié Salpêtrière, Université Pierre et Marie Curie GRC11-GRECHY, Paris, France.
authors: Veronique
authors: V
authors: Leblond
authors: Birmingham Heartlands Hospital, Birmingham, UK.
authors: Donald W
authors: DW
authors: Milligan
authors: University Hospitals Leuven, Leuven, Belgium.
authors: Ann
authors: A
authors: Janssens
authors: The Ohio State University, Columbus, OH, United States.
authors: Amy J
authors: AJ
authors: Johnson
authors: The Ohio State University, Columbus, OH, United States.
authors: Nyla A
authors: NA
authors: Heerema
authors: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors: Andreas
authors: A
authors: Bühler
authors: Department of Internal Medicine III, Ulm University, Ulm, Germany.
authors: Stephan
authors: S
authors: Stilgenbauer
authors: Sanofi, Bridgewater, NJ, United States.
authors: Jeanne
authors: J
authors: Devin
authors: University of Cologne, Cologne, Germany.
authors: Michael
authors: M
authors: Hallek
authors: The Ohio State University, Columbus, OH, United States. Electronic address: john.byrd@osumc.edu.
authors: John C
authors: JC
authors: Byrd
authors: The Ohio State University, Columbus, OH, United States.
authors: Michael R
authors: MR
authors: Grever
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D012008:Recurrence; D016019:Survival Analysis; D017211:Treatment Failure; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib; D014740:Vidarabine; C024352:fludarabine
keywords: Chronic lymphocytic leukemia; Cyclin dependent kinase inhibitor; Flavopiridol; Therapy; Tumor lysis syndrome