This is a phase 2, single-arm, open-label, multi-center study to establish the safety and efficacy of Troxatyl™ (troxacitabine) administered as a continuous infusion for 5 days to subjects with AML.

This is a phase 2, single-arm, open-label, multi-center study to establish the safety and efficacy of Troxatyl™ (troxacitabine) administered as a continuous infusion for 5 days to subjects with AML. The study will primarily assess the complete response (CR) rate of a 5-day continuous infusion of troxacitabine at 12 mg/m2/day given as second salvage therapy in adult patients with AML, with secondary objectives to determine the overall, relapse-free and event-free survival and remission duration; to determine the duration of response; to determine the complete response with incomplete platelet recovery (CRp) rate; to evaluate the tolerability and safety of 5-day continuous intravenous (IV) infusion of troxacitabine; and to determine the relationship between troxacitabine plasma concentrations, anti-leukemic activity and adverse events. Additional cycles of treatment may be given at the investigator's discretion, provided that the subject does not have progressive disease or experience a dose limiting toxicity. Bone marrow transplantation in responding subjects will be allowed.

Inclusion Criteria:

• Confirmed diagnosis of acute myeloid leukemia (AML) in the second salvage setting: refractory to two prior courses of therapy or primary refractory without response to two previous courses of leukemia therapy.

• Patients must have received at least two previous courses of induction chemotherapy to be considered in the second salvage setting.

• Patients who are in second relapse, must have had a duration of their second CR or CRp of less than six months.

• Subjects must have adequate organ and immune function as indicated by the following laboratory values:

  • Creatinine clearance ≥ 45 mL/min and ≤ 125 mL/min;
  • Total bilirubin ≤ 2.0 mg/dL (≤ 34.2 µmol/L);
  • AST (SGOT) and ALT (SGPT) ≤ 3 x upper limit of normal (ULN).
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of < 2, and an estimated life expectancy of at least eight weeks.

Exclusion Criteria:

• Clinical evidence of active central nervous system (CNS) leukemic involvement
• Active and uncontrolled infection
• Uncontrolled medical problems unrelated to the malignancy that impair patient ability to give informed consent or unacceptably reduce the safety of the proposed treatment
• Neurologic or psychiatric disorders that would interfere with informed consent or study follow-up
• Known or suspected intolerance or hypersensitivity to Troxatyl® or closely related compounds such as lamivudine or any of the stated ingredients
• A recent history of alcohol or other substance abuse
• Subjects who have used another investigational agent or participated in a clinical trial within the last 14 days prior to enrolment
• Females with a positive pregnancy test at screening
• Subjects who have previously been enrolled into this study and subsequently withdrew