Safety and Efficacy of Obatoclax Mesylate (GX15-070MS) in the Treatment of Myelofibrosis With Myeloid Metaplasia

A Multi-Center, Open-Label, Phase II Study of Single-Agent GX15-070MS Administered as a 24-Hour Infusion Every 2 Weeks to Patients With Myelofibrosis With Myeloid Metaplasia (MF)

Defects in the apoptotic process can lead to the onset of cancer by allowing cells to grow unchecked when an oncogenic signal is present. Obatoclax is designed to restore apoptosis through inhibition of the Bcl-2 family of proteins, thereby reinstating the natural process of cell death that is often inhibited in cancer cells.

This is a multi-center, open-label, Phase II study of single-agent obatoclax administered in 2-week cycles as a 24-hour infusion every 2 weeks at a fixed dose of 60 mg to patients with myelofibrosis. Infusions may be administered on an outpatient basis. No investigational or commercial agents or therapies other than those described in the protocol may be administered with the intent to treat the patient's malignancy. Supportive care measures including those directed at controlling symptoms resulting from myelofibrosis (blood products, growth factor, hydroxyurea, etc.) are allowed.

Inclusion Criteria:

• Histologically confirmed myelofibrosis with myeloid metaplasia.
• No limitations on allowable type and amount of prior therapy.
• Patients must have normal organ function.
• Must be willing to submit to blood sampling for planned PK and PD analyzes.
• Must have ability to understand and willingness to sign a written informed consent form.

Exclusion Criteria:

• No other agents or therapies administered with the intent to treat malignancy.
• Patients with prior exposure to obatoclax.
• Uncontrolled, intercurrent illness.
• Pregnant women and women who are breast feeding.