Tipifarnib, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
First received: January 7, 2005
Last updated: July 22, 2015
Last verified: July 2015

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 Intervention Phase
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: tipifarnib
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin [ Time Frame: minimum of 30 days per treatment cycle ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: All cycles ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics [ Time Frame: Day 6 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: April 2007
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tipifarnib with conventional induction and consolidation Drug: cytarabine Drug: daunorubicin hydrochloride Drug: tipifarnib

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.


Ages Eligible for Study:   56 Years and older
Genders Eligible for Study:   Both
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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00101153

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)
Study Chair: Joseph Brandwein, MD Princess Margaret Hospital, Canada
  More Information

Additional Information:
Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00101153     History of Changes
Other Study ID Numbers: PMH-PHL-026  CDR0000405840  NCI-6670 
Study First Received: January 7, 2005
Last Updated: July 22, 2015
Health Authority: United States: Food and Drug Administration

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:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on February 08, 2016