Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

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Brief Title

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

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Complete Remission (CR) Rate

Secondary Outcome

 Median Overall Survival (OS)

Condition

Adult Acute Megakaryoblastic Leukemia

Intervention

Tipifarnib

Study Arms / Comparison Groups

 Treatment (tipifarnib)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

21

Start Date

May 2011

Completion Date

November 2014

Primary Completion Date

November 2014

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
      

Gender

All

Ages

65 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jeffrey Lancet, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01361464

Organization ID

NCI-2011-02589

Secondary IDs

NCI-2011-02589

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Jeffrey Lancet, Principal Investigator, Moffitt Cancer Center


Verification Date

February 2015