Tipifarnib, Cytarabine, and Daunorubicin in Treating Older Patients With 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: NCT00101153
Recruitment Status : Completed
First Posted : January 10, 2005
Last Update Posted : July 23, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University Health Network, Toronto

January 7, 2005
January 10, 2005
July 23, 2015
April 2007
March 2010   (Final data collection date for primary outcome measure)
  • Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin [ Time Frame: minimum of 30 days per treatment cycle ]
  • Toxicity [ Time Frame: All cycles ]
  • Pharmacokinetics [ Time Frame: Day 6 ]
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Complete list of historical versions of study NCT00101153 on Archive Site
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Tipifarnib, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia
A Phase I Study Of Therapy With The Farnesyl Transferase Inhibitor R115777 (Zarnestra) Combined With Conventional Induction And Consolidation Chemotherapy For Previously Untreated Patients Over Age 55 With Acute Myeloid Leukemia (AML)

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

PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given with cytarabine and daunorubicin in treating older patients with acute myeloid leukemia.


  • Determine the maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin in older patients with previously untreated acute myeloid leukemia.
  • Determine the toxicity of this regimen in these patients.
  • Determine the pharmacokinetics of this regimen in these patients.

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

Induction therapy (1 course): Patients receive cytarabine IV continuously on days 1-7, daunorubicin IV on days 6-8, and oral tipifarnib twice daily on days 6-15 in the absence of unacceptable toxicity. Patients achieving complete remission proceed to consolidation therapy.

Consolidation therapy (1 course): After hematologic recovery, patients begin consolidation therapy 35-60 days after the start of induction therapy. Patients receive cytarabine, daunorubicin, and tipifarnib as in induction therapy.

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. A total of 10 patients are treated at the recommended phase II dose.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-28 patients will be accrued for this study within 1.5-22 months.

Phase 1
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Drug: cytarabine
  • Drug: daunorubicin hydrochloride
  • Drug: tipifarnib
Experimental: Tipifarnib with conventional induction and consolidation
  • Drug: cytarabine
  • Drug: daunorubicin hydrochloride
  • Drug: tipifarnib
Brandwein JM, Leber BF, Howson-Jan K, Schimmer AD, Schuh AC, Gupta V, Yee KW, Wright J, Moore M, MacAlpine K, Minden MD; NCI CTEP Protocol 6670. A phase I study of tipifarnib combined with conventional induction and consolidation therapy for previously untreated patients with acute myeloid leukemia aged 60 years and over. Leukemia. 2009 Apr;23(4):631-4. doi: 10.1038/leu.2008.341. Epub 2008 Dec 18.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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March 2010   (Final data collection date for primary outcome measure)


  • Diagnosis of acute myeloid leukemia (AML)

    • All subtypes, except acute promyelocytic leukemia, are allowed
    • At least 20% bone marrow or peripheral blood blasts OR biopsy-confirmed extramedullary disease
  • No cerebrospinal fluid involvement



  • 56 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • Not specified


  • See Disease Characteristics
  • WBC < 100,000/mm^3 (treatment with hydroxyurea allowed)


  • Bilirubin ≤ 1.25 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.0 times ULN


  • Creatinine < 1.7 mg/dL OR
  • Creatinine clearance ≥ 60 mL/min


  • LVEF ≥ 50%
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia


  • HIV negative
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to tipifarnib or imidazole drugs (e.g., ketoconazole, clotrimazole, or miconazole)
  • No ongoing or active infection


  • Not pregnant
  • Fertile patients must use effective contraception
  • Able to swallow oral medications
  • No other uncontrolled illness
  • No psychiatric illness or social situation that would preclude study compliance


Biologic therapy

  • Not specified


  • No prior chemotherapy for AML except hydroxyurea for cytoreduction
  • More than 4 weeks since prior chemotherapy except hydroxyurea (6 weeks for nitrosoureas or mitomycin) and recovered

    • At least 24 hours since prior hydroxyurea

Endocrine therapy

  • No concurrent dexamethasone


  • More than 4 weeks since prior radiotherapy and recovered
  • No prior radiotherapy > 3,000 cGy to marrow-producing areas


  • Not specified


  • No other concurrent investigational agents
  • No other concurrent antileukemic agents
  • No concurrent treatment with any of the following:

    • Ketoconazole
    • Itraconazole
    • Voriconazole
    • Clarithromycin
    • Erythromycin
    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Cyclosporine
    • Pimozide
    • Warfarin
    • Grapefruit juice
    • Simvastatin
    • Lovastatin
    • Atorvastatin
  • No concurrent magnesium- or aluminum-containing antacids within 2 hours before or after tipifarnib administration
Sexes Eligible for Study: All
56 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
CDR0000405840 ( Registry Identifier: PDQ (Physician Data Query) )
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University Health Network, Toronto
University Health Network, Toronto
National Cancer Institute (NCI)
Study Chair: Joseph Brandwein, MD Princess Margaret Hospital, Canada
University Health Network, Toronto
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP