A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma

Cancer Sci. 2015 Sep;106(9):1219-23. doi: 10.1111/cas.12735.

Abstract

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of peripheral T-lymphocytes with a poor prognosis. This multicenter, two-stage, single-arm, phase II study assessed the efficacy and safety of bortezomib in patients with relapsed/refractory ATL who received at least one regimen of chemotherapy. The primary endpoint was the best overall response rate (ORR), and secondary endpoints included safety, the best response by lesions, and progression-free survival (PFS). Fifteen patients were enrolled in the first stage of this study. One partial remission (PR) and five stable disease (SD) were observed as the best overall responses, and ORR was 6.7% (95% confidence interval (C.I.) 0.17-31.95%). Responses according to disease sites were one complete remission (CR) in peripheral blood, two PR in measurable targeted lesions, and two PR in skin lesions. Progression-free survival (PFS) was 38 (95% CI; 18-106) days. All patients developed ≥1 adverse events (AEs), and 80% of patients had ≥1 grade 3/4 AEs; however, no new safety findings were obtained. Although these results fulfilled the planned settings to proceed to the second stage, the coordinating committee decided to terminate this study because single agent activity did not appear to be very promising for this cohort of patients.

Keywords: Adult T-cell leukemia/lymphoma; bortezomib; nuclear factor-κB; proteasome inhibitor; salvage treatment.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Bortezomib / adverse effects
  • Bortezomib / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Male
  • Middle Aged
  • Remission Induction / methods

Substances

  • Antineoplastic Agents
  • Bortezomib