A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)

Inclusion Criteria:

Pathological Confirmation of the Diagnosis of AML, MDS
PMNs >= 1,000/ul
Platelets >= 30,000/ul
Hematocrit >= 27% and/or Hemoglobin >= 9 gm/dl unsupported
ECOG Performance Status 0-2
Patients must be able to give informed consent
Female patients of childbearing age must have negative pregnancy test
AST, ALT and Alkaline Phosphatase =<2.5 x normal
Bilirubin =< 1.5 x normal
Serum Creatinine =< 2.0 mg/dl or Creatinine Clearance >= 40 ml/min
Left Ventricular Ejection Fraction >= 25%

Patients with poor-risk AML or high-risk MDS who have completed both induction and consolidation chemotherapy; poor risk AML is defined by one or more of the following characteristics:

Antecedent Hematologic Disorder
AML Arising from MDS
Therapy-related AML
Age >= 60 (in absence of favorable cytogenetics)
Adverse Cytogenetics (i.e., -5/5q, -7/7q, +8, 20q-, 11q23 abnormalities, complex karyotype; other abnormalities may be considered at discression of study chair)
Hyperleukocytosis at diagnosis (Blasts >= 30,000/mm^3 at diagnosis in absence of favorable cytogenetics)

High Risk MDS is defined by one or more of the following characteristics:

RAEB and RAEB-t, with IPSS Score >= 1.5 (adverse cytogenetics, > 10% marrow blasts, cytopenias in at least 2 lineages): See Appendix E (Greenberg, et al. Blood 89:2079-2088,1997)36
CMML with > 5% marrow blasts
Therapy-related MDS

Exclusion Criteria:

Any previous treatment with ZARNESTRA
Ongoing participation in any Phase II or III clinical trial where DFS and OS are primary endpoints (unless patient is withdrawn from that trial)
Acute promyelocytic (FAB M3) subtype
Presence of (8;21) translocation or inversion 16 genotype as sole abnormality
Eligible for curative allogeneic stem cell transplantation
Known allergy to imidazole drugs (e.g., ketoconazole, miconazole)
Presence of Residual AML (> 5% marrow blasts) or MDS, as Determined by Morphology, Flow Cytometry, and/or Cytogenetics
Active, Uncontrolled Infection
Disseminated Intravascular Coagulation
Active CNS Leukemia
Concomitant Chemotherapy, Radiation Therapy or Immunotherapy
Women who are pregnant or lactating will not be eligible for this trial, as the investigational agent may be harmful to the developing fetus or nursing infant