CClinicalTrials.gg
Sign In
CompletedNCT01361464Updated Apr 8, 2015Results posted

Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

A Phase 2 interventional study of Tipifarnib and Laboratory Biomarker Analysis in Adult Acute Megakaryoblastic Leukemia, Adult Acute Monoblastic Leukemia and Adult Acute Monocytic Leukemia, sponsored by National Cancer Institute (NCI). Completed at 7 sites in United States. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2015-04-08.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
21
Allocation
Not applicable
Ages
65 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 21 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
65 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
21 participants (actual)

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.

    Drug: Tipifarnib · Other: Laboratory Biomarker Analysis

Interventions

  • DrugTipifarnib

    Given PO

    Also known as: R115777, Zarnestra

  • OtherLaboratory Biomarker Analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Complete Remission (CR) Rate

    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.

    Time frame: From first treatment through follow up period, an expected average of 12 months

Secondary outcomes

  1. Median Overall Survival (OS)

    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).

    Time frame: From first treatment through follow up period, an expected average of 12 months

  2. Median 1-Year Survival Rate

    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.

    Time frame: 1 year

  3. Number of Participants With Relapse Free Survival

    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.

    Time frame: 7 months

07

Results

Posted Jan 6, 2014
Limitations and caveats
Due to trial not meeting primary endpoint of at least 3 CR/CRi after 2 cycles, accrual was suspended. 1 year survival was not calculated, not relevant in the setting of a median survival of 6.6 months and with study not meeting its primary endpoint.

Participant flow

The Southeast Phase II Consortium (SEP2C) enrolled participants at 3 cancer centers in the United States. The study opened to accrual on 5/24/2011 and closed to accrual 07/25/2012. Further development of Tipifarnib in acute myeloid leukemia (AML) was terminated after the study failed to meet the primary endpoint.

Participant flow — Overall Study
MilestoneR115777 Therapy
Started21
Completed18
Not completed3
Withdrew: Death1
Withdrew: Withdrawal by subject2

Outcome measures

PrimaryComplete Remission (CR) Rate

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.

Time frame:
From first treatment through follow up period, an expected average of 12 months
Reported as:
Number · percentage of participants
Complete Remission (CR) Rate
percentage of participantsR115777 Therapy
Complete Remission (CR) Rate11
SecondaryMedian Overall Survival (OS)

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).

Time frame:
From first treatment through follow up period, an expected average of 12 months
Reported as:
Median · months
Median Overall Survival (OS)
monthsR115777 Therapy
Median Overall Survival (OS)6.6 (4.2 to NA)
SecondaryMedian 1-Year Survival Rate

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.

Time frame:
1 year

No measurements were reported for this outcome.

SecondaryNumber of Participants With Relapse Free Survival

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.

Time frame:
7 months
Reported as:
Number · participants
Number of Participants With Relapse Free Survival
participantsR115777 Therapy
Number of Participants With Relapse Free Survival2

Adverse events

Collected over 19 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
R115777 Therapy—7/21 (33.3%)17/21 (81%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventR115777 Therapy
Febrile neutropeniaBlood and lymphatic system disorders4/21
Lung infectionInfections and infestations2/21
Sinus tachycardiaCardiac disorders1/21
NauseaGastrointestinal disorders1/21
VomitingGastrointestinal disorders1/21
ChillsGeneral disorders1/21
FatigueGeneral disorders1/21
FeverGeneral disorders1/21
General disorders and administration site conditions - OtherGeneral disorders1/21
Infections and infestations - OtherInfections and infestations1/21
Most frequent other events
Showing 10 of 38
Most frequent other events
EventR115777 Therapy
Febrile neutropeniaBlood and lymphatic system disorders8/21
FatigueGeneral disorders8/21
NauseaGastrointestinal disorders7/21
White blood cell decreasedInvestigations7/21
AnorexiaMetabolism and nutrition disorders7/21
DiarrheaGastrointestinal disorders6/21
VomitingGastrointestinal disorders6/21
DyspneaRespiratory, thoracic and mediastinal disorders6/21
Platelet count decreasedInvestigations5/21
Rash maculo-papularSkin and subcutaneous tissue disorders5/21

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)R115777 Therapy
<=18 years0
Between 18 and 65 years0
>=65 years21
Age, Continuous
Age, Continuous(years)R115777 Therapy
Median75 (66 to 84)
Sex: Female, Male
Sex: Female, Male(Participants)R115777 Therapy
Female10
Male11
Region of Enrollment
Region of Enrollment(participants)R115777 Therapy
United States21
08

Study locations

7 sites
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Emory University/Winship Cancer Institute
    Atlanta, Georgia 30322, United States
  • Blood and Marrow Transplant Group of Georgia
    Atlanta, Georgia 30342, United States
  • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
    Baltimore, Maryland 21287, United States
  • Memorial Sloan-Kettering Cancer Center
    New York, New York 10065, United States
  • Weill Medical College of Cornell University
    New York, New York 10065, United States
  • University of North Carolina
    Chapel Hill, North Carolina 27599, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 8, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01361464
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
May 26, 2011
Start date
May 2011
Primary completion
Nov 2014
Completion
Nov 2014
Results posted
Jan 6, 2014
Last update
Apr 8, 2015

Study contacts

Jeffrey Lancet
principal investigator · Moffitt Cancer Center
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2015. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Leukemia→

Other studies from this sponsor

National Cancer Institute (NCI)

Start the discussion