Clinical trial NCT01361464: Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia
Official title: Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2011-05-26
Enrollment: 21
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete Remission (CR) Rate
timeFrame: From first treatment through follow up period, an expected average of 12 months
Secondary outcomes:
measure: Median Overall Survival (OS)
timeFrame: From first treatment through follow up period, an expected average of 12 months
measure: Median 1-Year Survival Rate
timeFrame: 1 year
measure: Number of Participants With Relapse Free Survival
timeFrame: 7 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: Moffitt Cancer Center
name: Jeffrey Lancet
role: PRINCIPAL_INVESTIGATOR
References: