Inclusion Criteria:

• Written informed consent

• Diagnosis of AML according to WHO classification (excluding APL) who have had a first CR lasting no longer than 12 months OR no initial CR, who are receiving their initial salvage. For the purposes of this study, the following considerations apply:

  • Subjects may have received one or two induction cycles provided both were with the same agents even if different doses were used.
  • Induction cycles should normally use agents and doses considered as standard of care for induction at the investigational site concerned. An induction cycle would normally require at least part of the induction regimen to consist of approved agents.
  • Subjects may have received consolidation for any number of cycles. Consolidation will be considered as any regimens given while the subject was in remission after 1-2 induction cycles.
  • Subjects who received hematopoietic stem cell transplant (HSCT) in first remission are eligible provided there has been no chemotherapy or other targeted therapies to treat a relapse. Donor leukocyte infusion (DLI) is allowed provided there is no evidence of hematologic relapse as defined by the International Working Group (IWG).
• Subjects should have recovered from the acute adverse effects of prior therapies to grade ≤1 (according to CTCAE v3) (excluding alopecia).
• Subjects should have not received prior therapy for first relapse or for refractory disease (a second induction cycle is allowed as defined above).
• Subjects must have bone marrow aspiration performed within four weeks prior to study entry showing the subject is neither a CR nor CRp. This may be done at the Screening visit if appropriate and feasible.

• Subjects must have adequate hepatic and renal function including the following:

  • Total bilirubin ≤ 1.5 x upper limit of normal.
  • AST and ALT ≤ 2.5 x upper limit of normal.
  • Serum creatinine ≤ 1.5 x upper limit of normal.
• Age ≥ 65 years.
• Performance status (PS) ≤ 2 (ECOG scale).
• Screening left ventricular ejection fraction (LVEF) ≥ 50%
• Subject is able to comply with all study procedures during the study including all visits and tests.
• Male subjects with female partners of reproductive potential must use acceptable contraceptive methods for the duration of time on study and continue to do so for a further 3 months after the end of tosedostat treatment.

Exclusion Criteria:

• Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of any other investigational agents within 2 weeks prior to trial entry (with the exception of hydroxyurea, which can be used during the first 2 months during treatment with tosedostat in subjects with rapidly proliferative disease).
• Subjects with APL (FAB type M3) or CML in blast crisis.
• Any co-existing medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study.
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.

• Significant cardiovascular disease defined as:

  • Congestive heart failure NYHA class 4
  • Unstable angina pectoris
  • History of myocardial infarction within 6 months prior to study entry
  • Presence of clinically significant valvular heart disease
  • Uncontrolled or clinically significant ventricular arrhythmia
  • Presence of clinically significant conduction defect on screening ECG
  • Uncontrolled hypertension (i.e., systolic BP >160mmHg, diastolic >90 mmHg in repeated measurements) despite adequate therapy
  • Clinically significant atrial fibrillation.
• Gastrointestinal disorders that may interfere with absorption of drug.
• Interstitial lung disease.
• Subjects with grade III-IV peripheral neuropathy [or central nervous system leukemia].