5-year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen.

Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)

PURPOSE: A randomized trial of oblimersen plus fludarabine/cyclophosphamide (OBL-FC; n = 120) versus FC (n = 121) was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The primary end point was met: the complete response (CR) rate, defined as complete or nodular partial response, was significantly greater with OBL-FC than with FC (17% v 7%; P = .025). Among patients with CR, response duration was significantly longer with OBL-FC than with FC (median not reached; > 36 months v 22 months; P = .03). Maximum benefit with OBL-FC, including a four-fold increase in CR rate and a survival benefit with 3 years of follow-up (hazard ratio, 0.53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients. METHODS: Poststudy CLL treatment information was collected. Patients were observed for survival for up to 5 years from the date of random assignment. RESULTS: Poststudy CLL treatment was balanced between arms. Intent-to-treat analysis of 5-year survival showed no significant between-treatment difference (hazard ratio, 0.87; P = .34). Among the greater than 40% of patients with complete or partial remission, a significant 5-year survival benefit was observed with OBL-FC (hazard ratio, 0.60; P = .038). Among patients with fludarabine-sensitive disease who had previously demonstrated maximum benefit with OBL-FC, the previously observed survival benefit improved: a 50% reduction in the risk of death was observed (P = .004). CONCLUSION: In relapsed/refractory CLL, OBL combined with FC offers patients who achieve complete or partial remission, as well as those who have fludarabine-sensitive disease, a significant survival benefit.

Full Text

Duke Authors

Cited Authors

  • O'Brien, S; Moore, JO; Boyd, TE; Larratt, LM; Skotnicki, AB; Koziner, B; Chanan-Khan, AA; Seymour, JF; Gribben, J; Itri, LM; Rai, KR

Published Date

  • November 1, 2009

Published In

Volume / Issue

  • 27 / 31

Start / End Page

  • 5208 - 5212

PubMed ID

  • 19738118

Pubmed Central ID

  • PMC5321078

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

Digital Object Identifier (DOI)

  • 10.1200/JCO.2009.22.5748


  • eng

Conference Location

  • United States