title: Efficacy and safety of clofarabine in relapsed and/or refractory non-Hodgkin lymphoma, including rituximab-refractory patients.
abstract: BACKGROUND
  Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients.
  
  
  METHODS
  In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m(2) to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression.
  
  
  RESULTS
  Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m(2) . The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed.
  
  
  CONCLUSIONS
  Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013).
authors.affiliation: Division of Hematology and Medical Oncology and Hematology and Oncology Fellowship Program, Advocate Lutheran General Hospital, Park Ridge, IL 60068, USA. Illinois. cnabhan@oncmed.net
authors.forename: Chadi
authors.initials: C
authors.lastname: Nabhan
authors.forename: Nancy
authors.initials: N
authors.lastname: Davis
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Bitran
authors.forename: Angel
authors.initials: A
authors.lastname: Galvez
authors.forename: Walter
authors.initials: W
authors.lastname: Fried
authors.forename: Kathy
authors.initials: K
authors.lastname: Tolzien
authors.forename: Susan
authors.initials: S
authors.lastname: Foss
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Dewey
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Venugopal
mesh_terms: D000227:Adenine Nucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D000077866:Clofarabine; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019233:Retreatment; D000069283:Rituximab; D016879:Salvage Therapy
chemical_list: D000227:Adenine Nucleotides; D058846:Antibodies, Monoclonal, Murine-Derived; D001087:Arabinonucleosides; D000069283:Rituximab; D000077866:Clofarabine