Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

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Brief Title

Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Official Title

Phase I Trial of R115777 (NSC 702818) in Relapsed, Refractory or High Risk Myeloid Leukemia

Brief Summary

      Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for
      cell growth. This phase I trial is studying the side effects and best dose of tipifarnib in
      treating patients with relapsed or refractory acute myeloid leukemia
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To define the maximum tolerated dose (MTD) of R115777 (tipifarnib) in patients with
      relapsed, refractory, or high risk myeloid leukemias treated according to this regimen.

      II. To assess the toxicity and preliminary assessment of efficacy of R115777 in patients with
      relapsed, refractory, or high risk myeloid leukemias.

      OUTLINE: This is a dose-escalation, multicenter study.

      Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. Courses repeat every 28
      days in the absence of unacceptable toxicity or disease progression. Patients achieving a
      complete response (CR) receive 2 additional courses beyond CR. Patients experiencing relapse
      after previously achieving CR may receive additional tipifarnib at the current dose level for
      newly registered patients.

      Cohorts of 3-6 patients receive escalating doses of tipifarnib until the MTD is determined.
      The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience
      dose-limiting toxicity.

      Patients are followed every 6 months for survival.

      PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for this study.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

MTD defined as the highest dose level in which six patients have been evaluated for toxicity with no more than one patient experiencing dose limiting toxicity (DLT) assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0


Condition

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome

Intervention

tipifarnib

Study Arms / Comparison Groups

 Treatment (tipifarnib)
Description:  Patients receive oral tipifarnib twice daily on days 1-7 and 15-21. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients achieving a CR receive 2 additional courses beyond CR. Patients experiencing relapse after previously achieving CR may receive additional tipifarnib at the current dose level for newly registered patients.

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

30

Start Date

October 2004


Primary Completion Date

May 2011

Eligibility Criteria

        Inclusion Criteria:

          -  Adult patients with acute myeloid leukemia (AML), excluding the M3 subtype (acute
             promyelocytic leukemia), that are not likely to respond to conventional therapy,
             including:

               -  Relapsed or refractory AML after one to three prior induction regimens (not
                  counting consolidation therapies while in CR, such as autologous transplant),

               -  Newly diagnosed AML in patients up to age-70 with poor risk features (unfavorable
                  cytogenetics or findings suggestive of prior myelodysplasia) not fit for standard
                  induction therapy, and

               -  Newly diagnosed AML patients age 70 - 75 not fit for standard therapy (without
                  history of prior myelodysplastic syndrome [MDS])

          -  Bone marrow and peripheral blood studies must be available for confirmation of
             diagnosis; cytogenetics, flow cytometry, and molecular studies (such as fms-related
             tyrosine kinase 3 [Flt-3] status) will be obtained as per standard practice

          -  Patients with active central nervous system (CNS) leukemia are NOT eligible

          -  Performance status of 60% or greater by the Karnofsky scale

          -  If induction chemotherapy has been attempted, a minimum of 4 weeks must have elapsed
             since the completion of prior chemotherapy in order to be eligible for this study;
             hydroxyurea for control of blasts is not counted as chemotherapy, and may be given up
             until 24 hours before starting R115777

          -  Patients may have had prior autologous transplant; they must be at least 100 days post
             transplant, and have had recovery of their counts with ANC > 1000 and platelets
             greater than 100K at some point post transplant, and be without active CMV or fungal
             disease

          -  Patients may have received prior radiation therapy as part of a transplant
             conditioning regimen; radiotherapy must have been completed at least 100 days prior to
             starting on R115777

          -  There are no minimum hematological parameter requirements prior to the first two
             cycles of R115777, as patients with AML and MDS are understood to have low ANC and
             platelet counts when the disease is active; however, patients with WBC greater than
             30,000 will receive hydroxyurea to reduce WBC to below 30,000 at which point they may
             begin treatment with R115777

          -  A pretreatment calculated creatinine clearance (absolute value) of >= 60 ml/minute or
             serum creatinine of < 1.5 x upper limit of normal is required

          -  Serum bilirubin =< 2.0 mg/dl

          -  SGOT and SGPT =< 2.5 times the institutional upper limits of normal

          -  Any condition causing inability to swallow pills given by mouth will render patients
             ineligible for the trial

          -  There must be no plans for the patient to receive concurrent hormonal, biologic, or
             radiation therapy

          -  Patients eligible, at the time of starting the drug, for curative therapeutic
             approaches (such as allogeneic transplant) are not eligible for the trial; however,
             patients who achieve CR or PR as a result of R115777 may go on to allogeneic
             transplant

          -  Patients must be informed of the investigational nature of this study and must sign
             and give written informed consent in accordance with institutional and federal
             guidelines

          -  Prior to the first patient registration, the notification of institutional review
             board approval for this study must be provided to the Data Coordinating Center at City
             of Hope

          -  Antacids are allowed but must not be taken concurrently with R115777; (there must be
             at least 2 hours between antacid intake and R115777 dosing)

          -  Pregnant or lactating women are excluded from this trial; all patients of
             child-bearing potential, both male and female, must be advised to practice adequate
             contraception; premenopausal women must have a negative pregnancy test prior to entry
             on this study
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Mark Kirschbaum, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00101296

Organization ID

NCI-2012-03078

Secondary IDs

PHI-47

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Mark Kirschbaum, Principal Investigator, City of Hope Medical Center


Verification Date

January 2013