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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)

Phase 1
18 Years
Not Enrolling

Thank you

Trial Information

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)

OBJECTIVES: I. Determine toxicities and pharmacokinetics of oral R115777 in adults with
refractory acute leukemia or accelerated or blastic phase chronic myelogenous leukemia. II.
Determine the effect of R115777 on farnesylation within leukemia cells. III. Determine any
clinical response (at least 50% decrease in circulating leukemia cells) to R115777 by these

OUTLINE: This is a dose escalation, multicenter study. Patients receive oral R115777 for
7-21 days. Patients who achieve complete response (CR) or partial response (PR) following
1-4 courses of treatment may receive up to 4 additional courses. Patients with stable
disease may receive another 7-21 day course. If CR or PR is then achieved, patients may
receive up to 4 additional courses. Cohorts of 6-12 patients receive escalating doses of
R115777 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
at which between 17% and 33% of patients experience dose limiting toxicity.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.

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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Judith E. Karp, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

June 1999

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • untreated adult acute lymphoblastic leukemia
  • untreated adult acute myeloid leukemia
  • adult acute promyelocytic leukemia (M3)
  • secondary acute myeloid leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



University of Rochester Cancer Center Rochester, New York  14642
Marlene & Stewart Greenebaum Cancer Center, University of Maryland Baltimore, Maryland  21201
University of Iowa College of Medicine Iowa City, Iowa  52242