Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

NCT ID: NCT01361464

Last Updated: 2015-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2014-11-30

Brief Summary

This phase II trial is studying how well tipifarnib works in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the complete remission (CR) rate in acute myeloid leukemia (AML) patients prospectively selected for tipifarnib (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.

SECONDARY OBJECTIVES:

I. To determine the median overall and 1-year survival of patients treated with this regimen II. To determine the median relapse-free survival of patients treated with this regimen.

III. To determine the safety of this regimen in these patients IV. To determine the immunophenotypic expression of RASGRP1 on baseline bone marrow blasts and assess correlation with PCR-based detection.

OUTLINE: This is a multicenter study.

Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Bone marrow aspirate and/or biopsy are collected at baseline and on day 28 of course 1 and 2 for RasGRP1 protein expression analysis by qRT-PCR.

After completion of study therapy, patients are followed up every 30 days.

Conditions

Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (tipifarnib)

Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Tipifarnib

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Tipifarnib

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

R115777; Zarnestra

Eligibility Criteria

Inclusion Criteria

• Previously untreated acute myeloid leukemia (AML) (de novo or secondary)

• No diagnosis of acute promyelocytic leukemia (APL)
• Deemed unsuitable for or refuses standard induction chemotherapy
• RASGRP1:APTX ratio >= 5, through bone marrow screening
• No patients with known leukemic involvement of the central nervous system
• ECOG performance status =< 2
• No WBC >= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
• Serum creatinine less than 1.5 times the upper limit of the normal range (ULN) (National Cancer Institute [NCI] Common Toxicity Criteria [CTC] Grade 1)
• Total bilirubin less than 1.5 times ULN (unless the increase is unequivocally due to hemolysis or Gilbert syndrome)
• ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)
• Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• No symptomatic neuropathy of grade 2 or worse
• No uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777), such as the imidazole drugs, including clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, ticonazole, or terconazole
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with R115777; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; known HIV-positive patients NOT on antiretroviral therapy AND with a CD4 cell count >= 400/mm^3 are eligible
• No other concurrent cytotoxic or biologic antileukemic therapy
• No patients who are receiving any other investigational agents
• Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) while taking tipifarnib (R115777) is contraindicated

• If clinically indicated, subjects may use non-enzyme-inducing anticonvulsants during treatment with R115777

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Lancet

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Emory University/Winship Cancer Institute

Atlanta, Georgia, United States

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Weill Medical College of Cornell University

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

NCI-2011-02589

Identifier Type: REGISTRY

Identifier Source: secondary_id

16572

Identifier Type: -

Identifier Source: secondary_id

CDR0000699713

Identifier Type: -

Identifier Source: secondary_id

8977

Identifier Type: OTHER

Identifier Source: secondary_id

8977

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA076292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00100

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02589

Identifier Type: -

Identifier Source: org_study_id

NCT01364038

Identifier Type: -

Identifier Source: nct_alias