Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

Tracking Information
First Submitted Date ICMJE	May 24, 2011
First Posted Date ICMJE	May 26, 2011
Results First Submitted Date	November 15, 2013
Results First Posted Date	January 6, 2014
Last Update Posted Date	April 8, 2015
Study Start Date ICMJE	May 2011
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 15, 2013)	Complete Remission (CR) Rate [ Time Frame: From first treatment through follow up period, an expected average of 12 months ]; Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count >/= 1,000/mm^3, Platelet count >/= 100,000/mm^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.
Original Primary Outcome Measures ICMJE; (submitted: May 25, 2011)	Number of Participants with Complete Remission [ Time Frame: From first treatment through follow up period, an expected average of 12 months ]; To determine the complete remission (CR) rate in AML patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. Patients will be periodically followed after their completion of the study to collect information on subsequent therapies and survival data.
Change History	Complete list of historical versions of study NCT01361464 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 15, 2013)	Median Overall Survival (OS) [ Time Frame: From first treatment through follow up period, an expected average of 12 months ]Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).; Median 1-Year Survival Rate [ Time Frame: 1 year ]Prior to the early discontinuation of the study (for not meeting the primary endpoint of at least 3 CR/CRi after 2 cycles), investigators had planned to calculate one year survival from Kaplan Meier estimates.; Number of Participants With Relapse Free Survival [ Time Frame: 7 months ]Relapse-free survival is calculated from the date of documentation of complete remission/morphologic complete remission with incomplete blood count recovery (CR/CRi) until disease relapse or death from any cause.
Original Secondary Outcome Measures ICMJE; (submitted: May 25, 2011)	Median Overall Survival (OS) Rate [ Time Frame: From first treatment through follow up period, an expected average of 12 months ]Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the CRF.; Median 1-Year Survival Rate [ Time Frame: Up to 12 months per participant ]One year survival will be calculated from Kaplan Meier estimates.; Number of Serious Adverse Events Reported That May be Related to Study Treatment [ Time Frame: From first treatment through follow up period, an expected average of 7 months ]All patients receiving R115777 will be evaluable for toxicity from the time of their first treatment with R115777, up through the 30-day follow up period after treatment termination, or until the initiation of subsequent therapy, whichever comes first.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
Official Title ICMJE	Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio
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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	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
Intervention ICMJE	Drug: Tipifarnib Given PO Other Names: R115777 Zarnestra; Other: Laboratory Biomarker Analysis Correlative studies
Study Arms	Experimental: 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.; Interventions: Drug: Tipifarnib; Other: Laboratory Biomarker Analysis
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 10, 2013)	21
Original Estimated Enrollment ICMJE; (submitted: May 25, 2011)	35
Actual Study Completion Date	November 2014
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	65 Years and older (Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01361464
Other Study ID Numbers ICMJE	NCI-2011-02589; NCI-2011-02589 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 16572; CDR0000699713; 8977 ( Other Identifier: Moffitt Cancer Center ); 8977 ( Other Identifier: CTEP ); P30CA076292 ( U.S. NIH Grant/Contract ); N01CM00071 ( U.S. NIH Grant/Contract ); U01CA070095 ( U.S. NIH Grant/Contract ); N01CM00100 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Cancer Institute (NCI)
Study Sponsor ICMJE	National Cancer Institute (NCI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Jeffrey Lancet Moffitt Cancer Center
PRS Account	National Cancer Institute (NCI)
Verification Date	February 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP