A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)

January 8, 2013 updated by: National Cancer Institute (NCI)

A Phase II Study of the Farnesyltransferase Inhibitor ZARNESTRA (Tipifarnib, R115777, NSC #702818, IND #58,359) in Complete Remission Following Induction and/or Consolidation Chemotherapy in Adults With Poor-Risk Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplasia (MDS).

Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Phase II trial to study the effectiveness of tipifarnib in treating patients who have acute myeloid leukemia or myelodysplastic syndrome in first complete remission

Study Overview

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the duration of disease-free survival (DFS) and overall survival (OS) when ZARNESTRA is administered after intensive induction and consolidation chemotherapy to adults with poor risk acute myelogenous leukemia (AML) or high-risk myelodysplasia (MDS) in first complete remission (CR).

SECONDARY OBJECTIVES:

I. To determine the tolerability and toxicities of ZARNESTRA when administered in a chronic dosing schedule over a 48 week period to adults in first CR following intensive cytotoxic chemotherapies.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 14-44 patients will be accrued for this study within 11-15 months.

Study Type

Interventional

Enrollment (Anticipated)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Baltimore, Maryland, United States, 21287-8936
        • Johns Hopkins University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pathological Confirmation of the Diagnosis of AML, MDS
  • PMNs >= 1,000/ul
  • Platelets >= 30,000/ul
  • Hematocrit >= 27% and/or Hemoglobin >= 9 gm/dl unsupported
  • ECOG Performance Status 0-2
  • Patients must be able to give informed consent
  • Female patients of childbearing age must have negative pregnancy test
  • AST, ALT and Alkaline Phosphatase =<2.5 x normal
  • Bilirubin =< 1.5 x normal
  • Serum Creatinine =< 2.0 mg/dl or Creatinine Clearance >= 40 ml/min
  • Left Ventricular Ejection Fraction >= 25%
  • Patients with poor-risk AML or high-risk MDS who have completed both induction and consolidation chemotherapy; poor risk AML is defined by one or more of the following characteristics:

    • Antecedent Hematologic Disorder
    • AML Arising from MDS
    • Therapy-related AML
    • Age >= 60 (in absence of favorable cytogenetics)
    • Adverse Cytogenetics (i.e., -5/5q, -7/7q, +8, 20q-, 11q23 abnormalities, complex karyotype; other abnormalities may be considered at discression of study chair)
    • Hyperleukocytosis at diagnosis (Blasts >= 30,000/mm^3 at diagnosis in absence of favorable cytogenetics)

High Risk MDS is defined by one or more of the following characteristics:

  • RAEB and RAEB-t, with IPSS Score >= 1.5 (adverse cytogenetics, > 10% marrow blasts, cytopenias in at least 2 lineages): See Appendix E (Greenberg, et al. Blood 89:2079-2088,1997)36
  • CMML with > 5% marrow blasts
  • Therapy-related MDS

Exclusion Criteria:

  • Any previous treatment with ZARNESTRA
  • Ongoing participation in any Phase II or III clinical trial where DFS and OS are primary endpoints (unless patient is withdrawn from that trial)
  • Acute promyelocytic (FAB M3) subtype
  • Presence of (8;21) translocation or inversion 16 genotype as sole abnormality
  • Eligible for curative allogeneic stem cell transplantation
  • Known allergy to imidazole drugs (e.g., ketoconazole, miconazole)
  • Presence of Residual AML (> 5% marrow blasts) or MDS, as Determined by Morphology, Flow Cytometry, and/or Cytogenetics
  • Active, Uncontrolled Infection
  • Disseminated Intravascular Coagulation
  • Active CNS Leukemia
  • Concomitant Chemotherapy, Radiation Therapy or Immunotherapy
  • Women who are pregnant or lactating will not be eligible for this trial, as the investigational agent may be harmful to the developing fetus or nursing infant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (tipifarnib)
Patients receive oral tipifarnib twice daily on days 1-14. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Given orally
Other Names:
  • R115777
  • Zarnestra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: 6 months
The trial is a success if greater than 45% of patients survive to 6 months. Comparing this to the null hypothesis of 25% survival, we have 84% power to detect this difference using an exact 2-sided binominal test of proportions for alpha of 0.10. This assumes no censoring occurs before 6 months.
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Tolerability and toxicities of ZARNESTRA when administrated in a chronic dosing schedule over a 48-week period to adults in first CR following intensive cytotoxic chemotherapy
Time Frame: Up to 48 weeks
Up to 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2002

Primary Completion (Actual)

October 1, 2007

Study Registration Dates

First Submitted

September 6, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 9, 2013

Last Update Submitted That Met QC Criteria

January 8, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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