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Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia

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

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome

Eligibility Criteria

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

Inclusion Criteria: Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts) ECOG performance status 0 or 1 Patients must be able to give informed consent SGOT and SGPT =< 2.5 x normal limits (grade 1) Serum creatinine =< 1.5 x normal limits (grade 1) AML (any of the following): Newly diagnosed AML in adults >= 75 years Newly diagnosed AML arising from MDS in adults >= 65 years Hyperleukocytosis with >= 30,000 leukemic blasts/uL Exclusion Criteria: Acute promyelocytic (FAB M3) subtype Previously treated with chemotherapy for leukemia (except for hydroxyurea) Disseminated intravascular coagulation (laboratory or clinical) Active central nervous system leukemia Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments Intrinsic impaired organ function (as stated above) Symptomatic neuropathy (grade 2 or worse) Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis

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 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.

Outcomes

Primary Outcome Measures

Complete remission (CR) rate
CR rates will be calculated with 95% confidence intervals for each age group separately.

Secondary Outcome Measures

Partial remission (PR) rate
Will be estimated by observed proportions and 95% confidence intervals.
Toxicity rates assessed using NCI CTCAE version 3.0
Will be estimated by observed proportions and 95% confidence intervals.
Duration of response
Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
Duration of survival
Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.

Full Information

First Posted
December 7, 2001
Last Updated
March 22, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00027872
Brief Title
Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Official Title
A Phase II Study of Farnesyl Transferase Inhibitor R115777 (Zarnestra) (R115777 ( Zarnestra), Tipifarnib, R115777, NSC #702818) in Elderly Patients With Previously Untreated Poor-Risk Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
October 2001 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
January 2009 (Actual)

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 older patients who have previously untreated acute myeloid leukemia
Detailed Description
PRIMARY OBJECTIVES: I. To determine the complete response rate of R115777 (tipifarnib) in previously untreated acute myeloid leukemia (AML) in (a) elderly patients (age >= 75) and (b) patients (age >= 65) with AML preceded by myelodysplastic syndrome (MDS), using a chronic dosing schedule. SECONDARY OBJECTIVES: I. To determine progression-free and overall survival in patients with previously untreated AML treated with R115777, using a chronic dosing schedule. II. To determine the duration of response in patients with previously untreated AML treated with R115777, using a chronic dosing schedule. III. To determine the effect of R115777 on the phosphorylation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K) in leukemic cells. IV. To determine the effect of R115777 on processing of the farnesylated protein HDJ-2. V. To determine the toxicities of R115777 when given in a chronic dosing schedule. OUTLINE: This is a multicenter study. Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy. Patients are followed for survival. PROJECTED ACCRUAL: A total of 125 patients will be accrued for this study within 11-17 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Erythroid Leukemia (M6), Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), 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(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Myelomonocytic Leukemia (M4), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Cellular Diagnosis, Adult Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Treatment (tipifarnib)
Arm Type
Experimental
Arm Description
Patients receive oral tipifarnib twice daily on days 1-21. Patients with a complete or partial response, hematologic improvement, or stable disease continue treatment every 29-63 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response after the second course of therapy receive 2 additional courses of therapy.
Intervention Type
Drug
Intervention Name(s)
tipifarnib
Other Intervention Name(s)
R115777, Zarnestra
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Complete remission (CR) rate
Description
CR rates will be calculated with 95% confidence intervals for each age group separately.
Time Frame
Up to 8 years
Secondary Outcome Measure Information:
Title
Partial remission (PR) rate
Description
Will be estimated by observed proportions and 95% confidence intervals.
Time Frame
Up to 8 years
Title
Toxicity rates assessed using NCI CTCAE version 3.0
Description
Will be estimated by observed proportions and 95% confidence intervals.
Time Frame
Up to 8 years
Title
Duration of response
Description
Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
Time Frame
From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 8 years
Title
Duration of survival
Description
Duration of response and survival will be summarized by the Kaplan-Meier estimate of the survival distribution.
Time Frame
From time of enrollment onto this study to the time of death, assessed up to 8 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologic confirmation of the diagnosis of AML (>= 20% marrow blasts) ECOG performance status 0 or 1 Patients must be able to give informed consent SGOT and SGPT =< 2.5 x normal limits (grade 1) Serum creatinine =< 1.5 x normal limits (grade 1) AML (any of the following): Newly diagnosed AML in adults >= 75 years Newly diagnosed AML arising from MDS in adults >= 65 years Hyperleukocytosis with >= 30,000 leukemic blasts/uL Exclusion Criteria: Acute promyelocytic (FAB M3) subtype Previously treated with chemotherapy for leukemia (except for hydroxyurea) Disseminated intravascular coagulation (laboratory or clinical) Active central nervous system leukemia Concomitant radiation therapy, chemotherapy, or immunotherapy; previous therapy for another malignancy is permitted, provided that at least 1 month has occurred since patient received any of these treatments Intrinsic impaired organ function (as stated above) Symptomatic neuropathy (grade 2 or worse) Known allergy to imidazole drugs, such as ketoconazole, miconazole, econazole, teconazole, clotrimazole, fenticonazole, isoconazole, sulconazole, or ticonazole Physical or psychiatric conditions that in the estimation of the principal investigator (PI) or designee place the patient at high risk of toxicity or non-compliance, e.g. severe congestive heart failure (CHF), unstable angina, or poorly controlled psychosis
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

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Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

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