S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

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Brief Title

S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

Official Title

Phase II Studies of Two Different Schedules and Two Different Doses of the Farnesyl Transferase Inhibitor R115777 (Tipifarnib, Zarnestra®, NSC-702818) for Previously Untreated Acute Myeloid Leukemia (AML) in Patients of Age 70 or Older

Brief Summary

      This randomized phase II trial is studying 4 different tipifarnib regimens to compare how
      well they work in treating older patients with acute myeloid leukemia. Tipifarnib may stop
      the growth of cancer cells by blocking the enzymes necessary for their growth
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To test whether any or all of four different regimens of R115777 (tipifarnib) is
      sufficiently effective therapy for previously untreated acute myeloid leukemia (AML) in
      patients of age 70 or older to warrant Phase III investigation. Additionally, to allow
      increased access for patients to an agent that appears promising in this patient population.

      II. To estimate the frequency and severity of toxicities of these regimens in this group of
      patients.

      III. To investigate in a preliminary manner the relationship of cytogenetics with response to
      R115777 (tipifarnib) and assess whether karyotype represents a potential prognostic factor
      among older AML patients who are not candidates for chemotherapy and are treated with
      R1157777.

      IV. To collect specimens for future correlations (e.g. RAS and downstream targets) to be
      identified at a later date.

      OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment
      arms.

      ARM I: Patients receive oral tipifarnib twice daily on days 1-21. ARM II: Patients receive
      oral tipifarnib twice daily on days 1-7 and 15-21. ARM III: Patients receive tipifarnib as in
      arm I, but at a lower dose. ARM IV: Patients receive tipifarnib as in arm II, but at a lower
      dose.

      In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease
      progression. Patients who achieve a complete remission (CR) receive up to 3 additional
      courses beyond CR. Patients in CR who develop recurrent disease after the completion of
      therapy are eligible to receive tipifarnib again.

      Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually
      for 3 years.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Total response rate, defined as the proportion of patients who achieve CR or PR


Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

tipifarnib

Study Arms / Comparison Groups

 Arm I
Description:  Arm I: Patients receive oral tipifarnib twice daily on days 1-21. In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Patients who achieve a complete remission (CR) receive up to 3 additional courses beyond CR. Patients in CR who develop recurrent disease after the completion of therapy are eligible to receive tipifarnib again.

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

296

Start Date

September 2004


Primary Completion Date

June 2006

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a morphologically confirmed diagnosis of acute myeloid leukemia
             (AML) with classification other than WHO Acute Promyelocytic Leukemia (FAB M3), based
             on bone marrow aspiration and biopsy performed within 14 days prior to registration;
             if a diagnostic biopsy has been performed within 28 days prior to registration, the
             marrow blast percentage is >= 70%, and no potentially anti-leukemic therapy has been
             given in the interim, then this bone marrow examination can be used for registration
             purposes; Note: This protocol uses the WHO diagnostic criteria for AML, not the FAB
             criteria; patients with WHO Acute Promyelocytic Leukemia (FAB M3) or blastic
             transformation of chronic myelogenous leukemia are not eligible; patients must not be
             candidates for or must have refused standard AML cytotoxic chemotherapy regimens

          -  Patients must not have received prior systemic chemotherapy for acute leukemia with
             the exception of hydroxyurea; patients must have a WBC =< 30,000/cmm within 1 day
             prior to registration; administration of hydroxyurea to control high WBC count prior
             to, during and after registration is permitted; patients with a history of prior
             myelodysplastic syndrome are eligible; however, prior treatment with AML induction
             type chemotherapy or high dose chemotherapy with hematopoietic stem cell support is
             not allowed; patients may have received hematopoietic growth factors, thalidomide,
             arsenic trioxide, signal transduction inhibitors, azacitidine, and low dose cytarabine
             for treatment of myelodysplastic syndrome; however, the dose of cytarabine must be <
             100 mg/M2/day; other low intensity therapies for MDS will also be permitted and should
             be discussed with the Study Coordinator; patients must be off prior therapy for MDS
             (excluding growth factors) and all toxicities must have resolved; if indicated, a
             single dose of intrathecal chemotherapy may also be given before or concurrent with
             induction chemotherapy

          -  Patient must have a bilirubin =< 1.5 x Institutional Upper Limit of Normal (IULN),
             unless the elevation is due primarily to elevated unconjugated hyperbilirubinemia
             secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction

          -  SGOT (AST) =< 2.5 x IULN, or SGPT (ALT) =< 2.5 x IULN, or both within 14 days prior to
             registration

          -  Patients must have a serum creatinine =< 1.5 x IULN within 14 days prior to
             registration

          -  Southwest Oncology Group patients must be registered on SWOG-9007, the cytogenetics
             protocol; collection of pretreatment marrow specimens must be completed within 14 days
             prior to registration; pretreatment specimens of bone marrow must be submitted to an
             approved Southwest Oncology Group Cytogenetics Laboratory for cytogenetic analysis;
             note that protocol SWOG-9007 also requires submission of remission and relapse
             specimens

          -  ECOG and CALGB have similar cytogenetics studies; please check with your group to find
             out about requirements for participation; CTSU sites will not be participating in
             SWOG-9007 and will not be submitting specimens for this study

          -  All patients must have cytogenetics performed and - if not registered to SWOG-9007 - a
             cytogenetics report submitted to the Cytogenetics Office at the Southwest Oncology
             Group Data Operations Center

          -  Southwest Oncology Group patients must be offered participation in S9910, the leukemia
             centralized reference laboratories and tissue repositories ancillary study; if consent
             is given, collection of pretreatment blood and/or marrow specimens must be completed
             within 14 days prior to registration; if the patient consents to participate in S9910,
             pretreatment specimens of marrow and/or peripheral blood must be submitted to the
             Southwest Oncology Group Myeloid Repository at the University of New Mexico for
             cellular and molecular studies; S9910 also requests submission of remission and
             relapse specimens

          -  ECOG and CALGB have similar reference laboratories and repository protocols; please
             check with your group to find out about requirements for participation

          -  CTSU sites will not be participating in S9910 and will not be submitting specimens for
             this study

          -  Patients of reproductive potential must have agreed to use an effective contraceptive
             method

          -  Patients with a prior malignancy are eligible; however, the patient must have
             completed all chemotherapy and radiotherapy at least 6 months prior to study
             registration; there should be no plan to begin therapy for the prior malignancy at the
             time of study registration; concurrent hormonal therapy is allowed

          -  Patients who are expected to require treatment with enzyme inducing antiepileptic
             drugs (EIAED) are not eligible for this study

          -  If day 14 or 30 falls on a weekend or holiday, the limit may be extended to the next
             working day; in calculating days of tests and measurements, the day a test or
             measurement is done is considered Day 0; therefore, if a test is done on a Monday, the
             Monday two weeks later would be considered Day 14; this allows for efficient patient
             scheduling without exceeding the guidelines

          -  All 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

          -  At the time of patient registration, the treating institution's name and ID number
             must be provided to the Data Operations Center in Seattle in order to ensure that the
             current (within 365 days) date of institutional review board approval for this study
             has been entered into the data base
      

Gender

All

Ages

70 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Harry Erba, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00093418

Organization ID

NCI-2012-03038

Secondary IDs

S0432

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Harry Erba, Principal Investigator, Southwest Oncology Group


Verification Date

January 2013