A Phase I Study to Determine Biological Endpoints of Up to 21 Day Dosing of the Farnesyltransferase Inhibitor R115777 (IND# 52,302) for Refractory and Relapsed Adult Leukemias (Summary Last Modified 9/1999)

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically or cytologically proven leukemia of any of the
following types: Acute myelogenous leukemia (AML) Newly diagnosed de novo AML in patients
over 60 years with poor risk features Antecedent hematologic disorder Complex karyotypes
or other adverse cytogenetics Stem cell immunophenotype AML arising from myelodysplastic
syndrome Secondary AML Recurrent or refractory AML, including primary induction failure
Acute lymphoblastic leukemia (ALL) Newly diagnosed de novo ALL in patients over 60 years
with poor risk disease features Complex karyotype or other adverse cytogenetics Mixed
lineage immunophenotype Recurrent or refractory ALL, including primary induction failure
Chronic myelogenous leukemia in accelerated phase or blast crisis No more than 2 prior
induction/reinduction therapy courses if failed primary induction therapy or relapsed
following complete remission Not eligible for or refused allogeneic bone marrow
transplantation Acute progranulocytic leukemia (M3) must meet following criteria: Prior
treatment with tretinoin required No coagulopathy Low risk for developing coagulopathy No
disseminated intravascular coagulation No CNS leukemia

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Not specified Hematopoietic: No hyperleukocytosis (at least 50,000 leukemic blasts/mm3)
Hepatic: Bilirubin normal SGOT and SGPT no greater than 2 times normal Renal: Creatinine
no greater than 2 times normal Cardiovascular: LVEF at least 45% by MUGA or echocardiogram
No myocardial infarction within the past 3 months No severe coronary artery disease No
cardiomyopathy No congestive heart failure No prior coagulation related sequelae: Deep
vein thrombosis Pulmonary embolus CNS thrombosis or bleed Other: No pregnant or nursing
Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 week since prior growth factors
(epoetin alfa, filgrastim, sargramostim, interleukin-3, interleukin-11) and recovered No
prior allogeneic bone marrow transplantation No concurrent immunotherapy Chemotherapy: See
Disease Characteristics At least 3 weeks since prior chemotherapy and recovered No other
concurrent chemotherapy Endocrine therapy: At least 3 weeks since prior endocrine therapy
and recovered Radiotherapy: At least 3 weeks since prior radiotherapy and recovered No
prior extensive radiotherapy to greater than 25% bone marrow No concurrent radiotherapy
Surgery: Not specified