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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

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Leukemia Drug: cytarabine Drug: daunorubicin hydrochloride Drug: tipifarnib Phase 1

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : April 2007
Actual Primary Completion Date : March 2010

Arm Intervention/treatment
Experimental: Tipifarnib with conventional induction and consolidation Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: tipifarnib

Primary Outcome Measures :
  1. Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin [ Time Frame: minimum of 30 days per treatment cycle ]
  2. Toxicity [ Time Frame: All cycles ]
  3. Pharmacokinetics [ Time Frame: Day 6 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   56 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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

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): NCT00101153

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Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 465
Sponsors and Collaborators
University Health Network, Toronto
National Cancer Institute (NCI)
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Study Chair: Joseph Brandwein, MD Princess Margaret Hospital, Canada

Publications of Results:
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Responsible Party: University Health Network, Toronto Identifier: NCT00101153    
Other Study ID Numbers: PMH-PHL-026
CDR0000405840 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 10, 2005    Key Record Dates
Last Update Posted: July 23, 2015
Last Verified: July 2015
Keywords provided by University Health Network, Toronto:
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myelomonocytic leukemia (M4)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
untreated adult acute myeloid leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors