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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)

Primary Purpose

Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
tipifarnib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Acute Myeloid Leukemia in Remission

Eligibility Criteria

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

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Ongoing participation in any Phase II or III clinical trial where DFS and OS are primary endpoints (unless patient is withdrawn from that trial) Acute promyelocytic (FAB M3) subtype Presence of (8;21) translocation or inversion 16 genotype as sole abnormality Eligible for curative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

Sites / Locations

  • Johns Hopkins University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (tipifarnib)

Arm Description

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.

Outcomes

Primary Outcome Measures

Disease-free survival
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.

Secondary Outcome Measures

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

Full Information

First Posted
September 6, 2002
Last Updated
January 8, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00045396
Brief Title
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)
Official Title
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).
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
June 2002 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), de Novo Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (tipifarnib)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
tipifarnib
Other Intervention Name(s)
R115777, Zarnestra
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Disease-free survival
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith Karp
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287-8936
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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)

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