Safety and Efficacy of Obatoclax Mesylate (GX15-070MS) for the Treatment of Hematological Malignancies

A Phase I Study of Obatoclax Mesylate (GX15-070MS) in Patients With Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myeloid Leukemia (CML)in Myeloid Blast Phase, Myelofibrosis, Previously-Treated Chronic Lymphocytic Leukemia (CLL), or Aplastic Anemia

Defects in the apoptotic process can lead to the onset of cancer by allowing cells to grow unchecked when an oncogneic 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 I study of obatoclax administered every 2-week or weekly cycles, or as a Prolonged Infusion every 2 to 3 weeks to patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Myeloid Leukemia (CML)in Myeloid Blast Phase, Myelofibrosis, Previously-Treated Chronic Lymphocytic Leukemia (CLL), or Aplastic Anemia. Due to the PK/PD sampling schedule Cycle 1 will require overnight hospitalization. For the following cycles treatment may be administered on an outpatient basis but is at the discretion of the investigator. No investigational or commercial agents or therapies other than those described within 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 hematological malignancies are allowed.

Inclusion Criteria:

• Histologically or cytologically confirmation of AML, MDS, CML in blast phase, myelofibrosis, CLL, or aplastic anemia
• There are no limitations on additional, allowable type and amount of prior therapy as long as acute toxicities have resolved to the allowable grade.
• Must have normal organ functions
• Must be willing to submit to blood sampling for the planned PK and PD analyses.
• Must have the ability to understand and willingness to sign a written informed consent form

Exclusion Criteria:

• No other agents or therapies administered for the intent to treat
• Uncontrolled, intercurrent illness
• Pregnant women and women who are breast feeding