Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis

Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):285-9. doi: 10.3816/CLML.2010.n.059.

Abstract

Background: Myelofibrosis (MF) is a disease characterized by the overexpression of the antiapoptotic BCL-2 family of proteins (eg, BCL-XL and MCL-1).

Patients and methods: We conducted a multicenter, open-label, noncomparative phase II study of obatoclax mesylate, a small-molecule pan-BCL-2 antagonist, in patients with MF. Obatoclax was administered as a 24-hour infusion (on an outpatient basis) every 2 weeks at a fixed dose of 60 mg.

Results: A total of 22 patients were enrolled, with a median age of 63 years (range, 43-89 years). Twelve were men, and all 22 patients were previously treated (median of 2 previous therapies). Ten patients (45%) had a Lille score of 1, and 9 patients (41%) had a Lille score of 2. Thirteen (59%) were red blood cell transfusion dependent. A median of 7 cycles of obatoclax were administered. No patient achieved complete or partial response according to International Working Group criteria. One patient (4%) demonstrated a clinical improvement (in terms of hemoglobin and platelet count) after 7 cycles of therapy. The improvement was sustained for 4 cycles of therapy, after which he underwent allogeneic stem cell transplantation. The most common adverse events included low-grade ataxia and fatigue in 50% of the patients. Dose reduction because of toxicity was required in 1 patient, whereas 2 patients were taken off the study because of grade 3 ataxia and grade 3 heart failure. Grade 3/4 anemia and thrombocytopenia were evident in 6 (27%) and 4 (18%) patients, respectively.

Conclusion: Obatoclax exhibits no significant clinical activity in patients with MF at the dose and schedule evaluated.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrroles
  • obatoclax