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

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
tipifarnib
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Iowa College of Medicine
  • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
  • University of Rochester Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
November 5, 2019
Sponsor
University of Maryland, Baltimore
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004009
Brief Title
R115777 in Treating Patients With Refractory or Recurrent Acute Leukemia or Chronic Myelogenous Leukemia
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)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
June 1999 (Actual)
Primary Completion Date
April 2001 (Actual)
Study Completion Date
April 2001 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
tipifarnib

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith E. Karp, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
University of Iowa College of Medicine
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Rochester Cancer Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States

12. IPD Sharing Statement

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

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