Study of Obatoclax in Previously Untreated Acute Myeloid Leukemia (AML)

A Multicenter, Open-Label, 2-Stage, Phase II Study of Single-Agent Obatoclax Mesylate Administered For Three Consecutive Days Every 2 Weeks to Older Patients With Previously Untreated Acute Myeloid Leukemia (AML)

This protocol will evaluate the efficacy of obatoclax in older patients with previously untreated AML.

The Pilot Safety portion of the study will evaluate the safety of obatoclax administered by a 3 hour infusion for 3 days in a row. The Pilot Schedule portion of the study will randomize 16 patients in to one of two cohorts: 1) patients receiving obatoclax administered by a 3 hour infusion for 3 days in a row or 2) patients receiving obatoclax administered by a 24 hour infusion for 3 days in a row. The schedule with the best overall efficacy and safety in the Pilot Schedule portion of the study will then be utilized in the Phase II portion of the study.

Inclusion Criteria:

• Histologically or cytologically confirmed AML

• No prior chemotherapy for AML (with the exception that the patients enrolled in the Pilot Safety evaluation may have had 1 prior therapy)

• Age ≥70 years

• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2

• Patients must have normal organ function as defined below:

  1. Total bilirubin < or = 2 mg/dL unless resulting from hemolysis,
  2. Aspartate transaminase (AST [SGOT])/alanine transaminase (ALT [SGPT]) < or = 2.5 x institutional ULN
  3. Creatinine within normal institutional limits, OR creatinine clearance > or = 50 mL/min/1.73 meters squared for patients with creatinine levels above institutional ULN

Exclusion Criteria:

• Patients who have received or are receiving any other investigational or commercial agents or therapies administered with the intent to treat their malignancy (with the exception that the patients enrolled in the pilot safety evaluation may have had 1 prior therapy)
• patients with history of allergic reactions attributed to components of the formulated product (PEG300 and polysorbate 20)
• patients with history of seizure disorders or central nervous system leukemia
• patients with uncontrolled, intercurrent illness including, but not limited to, symptomatic neurological illness; active, uncontrolled, systemic infection considered opportunistic, life-threatening, or clinically significant at the time of treatment; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; significant pulmonary disease or hypoxia; or psychiatric illness/social situations that would limit compliance with study requirements
• Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy