Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome

Inclusion Criteria:

- Patients must have histologically MDS (including French-American-British [FAB] types
refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory
anemia with excess blasts [RAEB], refractory anemia with excess blasts in
transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose
of the study, all patients will be classified by World Health Organization (WHO)
criteria

- By these criteria, FAB RA are split into:

- Pure dyserythropoietic refractory anemia (PRA)

- Refractory cytopenia with multilineage dysplasia (RCMD)

- FAB RARS is split into:

- Pure sideroblastic anemia (PSA)

- Refractory sideroblastic cytopenia with multilineage dysplasia (RSCMD)

- FAB RAEB is split into:

- RAEB I (< 10% BM blasts)

- RAEB II (10-20% BM blasts)

- Patients with CMMoL, and RAEBT by FAB classification will be included in the
protocol

- Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria

- =< 2 prior therapies

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Life expectancy of greater than 12 weeks

- Bilirubin =< 1.5mg %

- Creatinine =< 1.5mg %

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry and for the
duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for
UCN01) prior to entering the study or those who have not recovered from adverse
events due to agents administered more than 4 weeks earlier

- Patients may not be receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to R115777 (such as imidazoles)

- Patients eligible for bone marrow transplant (=< 60 years old), with a compatible
sibling, no contraindications for transplant

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with R115777.

- Growth factors other than filgrastim (G-CSF) are excluded; patients should be off
excluded growth factors for 2 weeks