Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma

Ann Oncol. 2004 Sep;15(9):1413-8. doi: 10.1093/annonc/mdh359.

Abstract

Background: The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C alpha in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL).

Patients and methods: Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle.

Results: The median age of the patients was 53 years (range 37-77). Histological subtypes were low-grade follicular lymphoma (n = 22) and B-cell small lymphocytic lymphoma (n = 4). Twenty-one (81%) had stage III/IV disease. The median number of previous lines of chemotherapy was two (range one to six). A total of 87 cycles of ISIS 3521 were administered. Twenty-three patients were assessable for response. Three patients achieved a partial response. No complete responses were observed. Ten patients had stable disease. Grade 3-4 toxicity was as follows: neutropenia (3.8%) and thrombocytopenia (26.9%).

Conclusions: ISIS 3521 has demonstrated anti-tumour activity in patients with relapsed low-grade NHL. There may be a potential role for this agent in combination with conventional chemotherapy for advanced low-grade lymphoma, and further trials are warranted.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Fever / chemically induced
  • Headache / chemically induced
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasm Staging
  • Oligodeoxyribonucleotides, Antisense / adverse effects
  • Oligodeoxyribonucleotides, Antisense / therapeutic use*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism
  • Protein Kinase C-alpha
  • Thionucleotides / adverse effects
  • Thionucleotides / therapeutic use*
  • Treatment Outcome

Substances

  • Oligodeoxyribonucleotides, Antisense
  • Thionucleotides
  • ISIS 3521
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha