R115777 in Treating Patients With Refractory or Recurrent Acute Leukemia or Chronic Myelogenous Leukemia

Sponsor
University of Maryland, Baltimore (Other)
Overall Status
Completed
CT.gov ID
NCT00004009
Collaborator
National Cancer Institute (NCI) (NIH)
3
22

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of R115777 in treating patients who have refractory or recurrent acute leukemia or chronic myelogenous leukemia.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

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 patients.

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.

Study Design

Study Type:
Interventional
Primary Purpose:
Treatment
Official Title:
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)
Actual Study Start Date :
Jun 1, 1999
Actual Primary Completion Date :
Apr 1, 2001
Actual Study Completion Date :
Apr 1, 2001

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 120 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Iowa College of Medicine Iowa City Iowa United States 52242
    2 Marlene & Stewart Greenebaum Cancer Center, University of Maryland Baltimore Maryland United States 21201
    3 University of Rochester Cancer Center Rochester New York United States 14642

    Sponsors and Collaborators

    • University of Maryland, Baltimore
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Judith E. Karp, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Maryland, Baltimore
    ClinicalTrials.gov Identifier:
    NCT00004009
    Other Study ID Numbers:
    • MSGCC-9802
    • CDR0000067221
    • MSGCC-0398115
    • URCC-980300
    • NCI-T99-0030
    First Posted:
    Aug 27, 2004
    Last Update Posted:
    Nov 7, 2019
    Last Verified:
    Nov 1, 2019

    Study Results

    No Results Posted as of Nov 7, 2019