AML
Conditions
Interventions
Patients with AML, meeting all eligibility criteria will be randomized on entry between:
Arm A: 2 induction cycles of daunorubicin (DNR) 45 mg/m^2/day, days 1-3 and cytarabine (Ara-C) 200 mg/m^2/day,
or
Arm B: 2 induction cycles of DNR 35 mg/m^2/day, days 1-3
Ara-C 200 mg/m^2/day, days 1-7
and PSC-833 loading dose 2 mg/kg over 2 hours, followed by 10 mg/kg/day, days 1-3
Patients in CR will then be given one consolidation cycle without PSC-833 consisting of Ara-C, mitoxantrone and etoposide.
Sponsors
Novartis Pharma AG
CH-4002 Basel
Switzerland
Eligibility
Inclusion criteria
Inclusion criteria: 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.
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Complete remission; 2. Disease-free survival; 3. Overall survival; 4. Association between complete remission and expression of P-gp by AML-blasts. | — |
Contacts
Public ContactB. Löwenberg
Erasmus Medical Center, Daniel den Hoed Cancer Center, Department of Hematology, P.O. Box 5201
Outcome results
None listed