Combination Chemotherapy and Tipifarnib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00124644
Recruitment Status : Terminated (Withdrawn due to "toxicity" problems)
First Posted : July 28, 2005
Last Update Posted : May 3, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as cytarabine, daunorubicin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with tipifarnib may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given together with combination chemotherapy in treating patients with newly diagnosed acute myeloid leukemia.

Condition or disease Intervention/treatment Phase
Leukemia Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: tipifarnib Procedure: chemotherapy Procedure: enzyme inhibitor therapy Procedure: high-dose chemotherapy Phase 1

Detailed Description:



  • Determine the maximum tolerated dose of tipifarnib when given in combination with induction therapy comprising cytarabine, daunorubicin, and etoposide followed by consolidation therapy comprising high-dose cytarabine in patients with newly diagnosed high-risk acute myeloid leukemia.


  • Determine the qualitative and quantitative toxic effects of this regimen, in terms of organ specificity, time course, predictability, and reversibility, in these patients.
  • Determine the rate of complete remission in patients treated with this regimen.
  • Determine the remission duration, overall survival, and relapse-free and event-free survival of patients treated with this regimen.
  • Determine the pharmacokinetics of this regimen in these patients.
  • Correlate pharmacodynamic measurements and levels of tumor necrosis factor-alpha with clinical response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of tipifarnib.

  • Induction therapy: Patients receive cytarabine IV continuously on days 1-7; daunorubicin IV and etoposide IV over 2 hours on days 5-7; and oral tipifarnib twice daily on days 5-12.

Patients undergo bone marrow biopsy on day 17 OR days 17 and 24 (if day 17 bone marrow biopsy shows suspicious disease). Patients achieving a complete remission (CR) proceed to consolidation therapy. Patients with residual disease, defined as > 5% leukemic blasts in a bone marrow of ≥ 20% cellularity, receive a second course of induction therapy comprising cytarabine IV continuously on days 1-5; daunorubicin IV and etoposide IV over 2 hours on days 4 and 5; and oral tipifarnib twice daily on days 4-9. Patients achieving a CR after a second course of induction therapy proceed to consolidation therapy. Patients not achieving a CR after a second course of induction therapy are removed from the study.

Cohorts of 3-6 patients receive escalating doses of tipifarnib until the maximum tolerated dose (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. An additional 12 patients are treated at the MTD.

  • Consolidation therapy: Patients receive high-dose cytarabine IV twice daily on days 1, 3, and 5. Treatment repeats approximately every 6-8 weeks for 4 courses.

After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 10-15 months.

Study Type : Interventional  (Clinical Trial)
Enrollment : 30 participants
Primary Purpose: Treatment
Official Title: A Phase I Study of R115777 (Zarnestra) in Combination With Induction Chemotherapy in Patients With Newly Diagnosed, High Risk Acute Myeloid Leukemia
Study Start Date : March 2006
Actual Primary Completion Date : December 2007
Actual Study Completion Date : January 2008

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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed acute myeloid leukemia (AML) according to the WHO classification system

    • High-risk disease
    • Newly diagnosed disease
    • Patients with secondary AML due to prior chemotherapy for a different malignancy are eligible
  • No known inv(16), t(8;21), or t(15;17) cytogenetic abnormality
  • No acute promyelocytic leukemia
  • No CNS leukemia



  • 18 to 59

Performance status

  • ECOG 0-2

Life expectancy

  • More than 6 months


  • Not specified


  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal


  • Creatinine normal OR
  • Creatinine clearance ≥ 60 mL/min


  • Ejection fraction > 50% by echocardiogram or MUGA
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia


  • No known HIV positivity
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to tipifarnib
  • No allergy to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)
  • No ongoing or active infection


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance


Biologic therapy

  • No concurrent epoetin alfa


  • See Disease Characteristics
  • No prior chemotherapy for AML or myelodysplastic syndromes except hydroxyurea

Endocrine therapy

  • Not specified


  • No concurrent palliative radiotherapy


  • Not specified


  • More than 30 days since prior investigational agents
  • No other concurrent investigational or commercial agents or therapies for the malignancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00124644

United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: William G. Blum, MD Ohio State University Comprehensive Cancer Center Identifier: NCT00124644     History of Changes
Other Study ID Numbers: CDR0000437105
First Posted: July 28, 2005    Key Record Dates
Last Update Posted: May 3, 2013
Last Verified: January 2008

Keywords provided by National Cancer Institute (NCI):
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(16;16)(p13;q22)
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic