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Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio

Phase 2
65 Years
Open (Enrolling)
Acute Myelogenous Leukemia

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Trial Information

Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio

This study will test the ability of a newly developed screening test, the RASGRP1:aprataxin
(APTX) ratio, to identify patients who are more likely to benefit from R115777 therapy.
RASGRP1 and APTX are genes that are expressed in leukemia cells. This test is performed on a
sample of bone marrow tissue, and determines the ratio of RASGRP1 and APTX expression in the
bone marrow. Ratios that are C5 are will be considered as a positive result, and these
patients will be eligible for treatment with R115777. The ratio of C5 is expected to be
found in about 30% of patients. This screening test is still considered an experimental

Inclusion Criteria:

- Age ≥ 65 with previously untreated AML (de novo or secondary)

- Deemed unsuitable for or refuses standard induction chemotherapy

- RASGRP1:APTX ratio ≥5, through bone marrow screening

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2

- Patients must have normal organ function as defined below:

- 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 (CTC Grade 1), unless the increase is
unequivocally due to hemolysis or Gilbert's Syndrome

- Alanine transaminase (ALT) and aspartate transaminase (AST) less than 2.5 times ULN
(CTC Grade 1)

- Ability to understand and the willingness to sign a written informed consent document

- The effects of R115777 (ZARNESTRA) on the developing human fetus are unknown. For
this reason and because farnesyl transferase inhibitor (FTI) agents as well as other
therapeutic agents used in this trial are known to be teratogenic, 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.

Exclusion Criteria:

- Diagnosis of acute promyelocytic leukemia (APL)

- Patients who are receiving any other investigational agents

- Patients with known leukemic involvement of the central nervous system

- Patients with white blood cells (WBC) ≥ 30,000/uL (hydroxyurea permitted up to 24
hours prior to initiation of therapy)

- Symptomatic neuropathy of grade 2 or worse

- Uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to R115777, such as the imidazole drugs, including clotrimazole,
ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole,
tioconazole or terconazole

- Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital,
primidone, carbamazepine, oxcarbazepine) while taking R115777 is contraindicated. If
clinically indicated, subjects may use nonenzyme-inducing anticonvulsants during
treatment with R115777.

- 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 human immunodeficiency virus (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/mm³ are

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants with Complete Remission

Outcome Description:

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.

Outcome Time Frame:

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

Safety Issue:


Principal Investigator

Jeffrey Lancet, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:

NCI # 8977



Start Date:

May 2011

Completion Date:

June 2014

Related Keywords:

  • Acute Myelogenous Leukemia
  • AML
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
University of Chicago Medical CenterChicago, Illinois  60637
University of Maryland Medical CenterBaltimore, Maryland  21201-1595
Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterBaltimore, Maryland  21231
Emory - Winship Cancer InstituteAtlanta, Georgia  30322
Cornell - Weill Medical College of Cornell UniversityNew York, New York  10065
UNC-Lineberger Comprehensive Cancer CenterChapel Hill, North Carolina  27599