An open label randomized controlled study in elderly subjects with previously untreated acute myelogenous leukaemia, comparing treatment groups randomised to receive daunorubicin and cytarabine or daunorubicin, cytarabine and PSC-833.

1. Age >= 60 years;

2. Subjects who have a cytopathologically confirmed diagnosis of previously untreated AML (M0-M2 and M4-M7, FAB classification);

3. Subjects with secondary AML progressing from antecedent MDS are eligible if there has been no previous chemotherapy. Antecedent MDS is defined as any antecedent haematological disease of at least 4 months duration;

4. WHO performance status <= 2;

5. Subjects have given written informed consent.

1. Cytopathologically confirmed CNS infiltration. NB: in the absence of clinical suspicion of CNS involvement, lumbar puncture is not required;

2. Subjects have had previous Polycythemia Rubra Vera, primary myelofibrosis, are in blast cell crisis of chronic myeloid leukaemia or are M3 AML according to FAB classification;

3. Subject has neurosensory toxicity >= Grade 2 (NCIC Expanded CTC);

4. Subject has neurocerebellar toxicity >= Grade 1 (NCIC Expanded CTC);

5. Subject is known to be positive for human immunodeficiency virus (HIV) type 1 antibody (testing to determine HIV antibody status is not necessary to be eligible);

6. Subject has impairment of hepatic or renal function as defined by the following baseline laboratory values:

ALT and/or AST >= 2.5 times IULN

Alkaline phosphatase >= 2.5 times IULN

Serum total bilirubin >= 1.5 times IULN

Serum creatinine >= 1.5 times IULN after adequate hydration;

7. Subject is currently receiving treatment with any of the agents listed in Appendix 11 if treatment cannot be discontinued at the specified time relative to PSC-833 administration. All of the drugs listed are well substantiated to interact with cyclosporin A;

8. Subject has had major surgery within 2 weeks of study entry;

9. Subject has received investigational therapy within 30 days of study entry;

10. Subject has known hypersensitivity to cyclosporin A;

11. Subject has received prior radiotherapy within 4 weeks of study entry;

12. Subject is < 5 years free of another primary malignancy with the exception of basal cell carcinoma of the skin and stage 1 cervical carcinoma;

13. Subject has previously been treated with chemotherapy for AML;

14. Subject has concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension etc.);

15. Subject has a psychological, intellectual or sensory dysfunction which is likely to impede their ability to understand and comply with study requirements;

16. Subject had a myocardial infarction within the last 6 months, has symptomatic ischaemic heart disease, congestive heart failure or other uncontrolled coronary disease.