A Phase II Study of the Farnesyltransferase Inhibitor ZARNESTRA (Tipifarnib, 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primary endpoints (unless patient is withdrawn from that trial)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