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

Sameer A. Parikh, Hagop Kantarjian, Aaron Schimmer, William Walsh, Ekatherine Asatiani, Khaled El-Shami, Elliott Winton, Srdan Verstovsek

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)285-289
Number of pages5
JournalClinical Lymphoma, Myeloma and Leukemia
Volume10
Issue number4
DOIs
StatePublished - Aug 2010

Keywords

  • Ataxia
  • Polycythemia vera
  • Post-essential thrombocythemia myelofibrosis
  • Targeted therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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