title: Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial.
abstract: OBJECTIVE
  To compare the receipt of clofarabine plus cytarabine (Clo+Ara-C arm) with cytarabine (Ara-C arm) in patients ≥ 55 years old with refractory or relapsed acute myelogenous leukemia (AML).
  
  
  METHODS
  Patients were randomly assigned to receive either clofarabine (Clo) 40 mg/m(2) or a placebo followed by Ara-C 1 g/m(2) for five consecutive days. The primary end point was overall survival (OS). Secondary end points included event-free survival (EFS), 4-month EFS, overall remission rate (ORR; complete remission [CR] plus CR with incomplete peripheral blood count recovery), disease-free survival (DFS), duration of remission (DOR), and safety.
  
  
  RESULTS
  Among 320 patients with confirmed AML (median age, 67 years), the median OS was 6.6 months in the Clo+Ara-C arm and 6.3 months in the Ara-C arm (hazard ratio [HR], 1.00; 95% CI, 0.78 to 1.28; P = 1.00). The ORR was 46.9% in the Clo+Ara-C arm (35.2% CR) versus 22.9% in the Ara-C arm (17.8% CR; P < .01). EFS (HR: 0.63; 95% CI, 0.49 to 0.80; P < .01) and 4-month EFS (37.7% v 16.6%; P < .01) favored the Clo+Ara-C arm compared with Ara-C arm, respectively. DFS and DOR were similar in both arms. Overall 30-day mortality was 16% and 5% for CLO+Ara-C and Ara-C arms, respectively. In the Clo+Ara-C and Ara-C arms, the most common grade 3 to 4 toxicities were febrile neutropenia (47% v 35%, respectively), hypokalemia (18% v 11%, respectively), thrombocytopenia (16% v 17%, respectively), pneumonia (14% v 10%, respectively), anemia (13% v 0%, respectively), neutropenia (11% v 9%, respectively), increased AST (11% v 2%, respectively), and increased ALT (10% v 3%, respectively).
  
  
  CONCLUSIONS
  Although the primary end point of OS did not differ between arms, Clo+Ara-C significantly improved response rates and EFS. Study follow-up continues, and the role of clofarabine in the treatment of adult patients with AML continues to be investigated.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA. sfaderl@mdanderson.org
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.forename: Gary
authors.initials: G
authors.lastname: Schiller
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
authors.forename: Robert
authors.initials: R
authors.lastname: Stuart
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Ganguly
authors.forename: David
authors.initials: D
authors.lastname: Avigan
authors.forename: Michael
authors.initials: M
authors.lastname: Craig
authors.forename: Robert
authors.initials: R
authors.lastname: Collins
authors.forename: Michael
authors.initials: M
authors.lastname: Maris
authors.forename: Tibor
authors.initials: T
authors.lastname: Kovacsovics
authors.forename: Stuart
authors.initials: S
authors.lastname: Goldberg
authors.forename: Karen
authors.initials: K
authors.lastname: Seiter
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Hari
authors.forename: Jochen
authors.initials: J
authors.lastname: Greiner
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
authors.forename: Michael
authors.initials: M
authors.lastname: Vasconcelles
authors.forename: Dirk
authors.initials: D
authors.lastname: Huebner
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage*; D000077866:Clofarabine; D003561:Cytarabine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012008:Recurrence
chemical_list: D000227:Adenine Nucleotides; D001087:Arabinonucleosides; D010919:Placebos; D003561:Cytarabine; D000077866:Clofarabine