title: Oral clofarabine for relapsed/refractory non-Hodgkin lymphomas: results of a phase 1 study.
abstract: We conducted a phase 1 trial evaluating the oral nucleoside analog clofarabine in patients with relapsed/refractory non-Hodgkin lymphoma. Patients were treated once daily on days 1 through 21 of a 28-day cycle for a maximum of six cycles. The study was conducted with a 3 + 3 design with 10 additional patients treated at the recommended phase 2 dose. Thirty patients were enrolled including indolent B-cell lymphomas (n = 21), mantle cell lymphoma (n = 6) and diffuse large B-cell lymphoma (n = 3). The primary toxicities were hematologic including grade 3-4 neutropenia (53%) and thrombocytopenia (27%). Three milligrams was determined to be the recommended phase 2 dose. Tumor volume was reduced in 70% of patients, and the overall response rate was 47% including 27% complete remissions. Responses were seen in indolent B-cell lymphomas and mantle cell lymphoma. At a median follow-up of 17 months, 68% of responding patients remain in ongoing remission. Oral clofarabine was well tolerated with encouraging efficacy in indolent B-cell lymphomas and mantle cell lymphomas, warranting further investigation.
authors.affiliation: Center for Lymphoma, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. jabramson@partners.org
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Abramson
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Takvorian
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jacobsen
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Brown
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Barnes
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: Ephraim P
authors.initials: EP
authors.lastname: Hochberg
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D000077866:Clofarabine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D000077866:Clofarabine