Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: November 9, 2004
Last updated: May 9, 2014
Last verified: June 2013
This phase I/II trial is studying the side effects and best dose of tipifarnib when given with idarubicin and cytarabine and to see how well it works in treating patients with newly diagnosed myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Tipifarnib (Zarnestra) may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Giving idarubicin and cytarabine with tipifarnib may kill more cancer cells.

Condition Intervention Phase
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)
Childhood Myelodysplastic Syndromes
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndromes
Refractory Anemia With Excess Blasts
Refractory Anemia With Excess Blasts in Transformation
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Untreated Adult Acute Myeloid Leukemia
Drug: cytarabine
Drug: idarubicin
Drug: tipifarnib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Participants With Complete Response [ Time Frame: 21 Day Cycle ]
    Complete Response (CR) is required bone marrow blasts ≤5% and recovery of normal hematopoiesis with an absolute neutrophil count (ANC) of 1*10^9/L or more and platelet count of 100*10^9/L or more; and a complete response without platelets (CRp) is the same criteria as CR but with platelet counts from 20*10^9/L to less than 100*10^9/L.

Enrollment: 95
Study Start Date: September 2004
Study Completion Date: February 2010
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
See Detailed Description
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: idarubicin
Given IV
Other Names:
  • 4-demethoxydaunorubicin
  • 4-DMDR
  • DMDR
  • IDA
Drug: tipifarnib
Given orally
Other Names:
  • R115777
  • Zarnestra

Detailed Description:


I. To determine the tolerability of the combination of R115777 (Zarnestra™) and Idarubicin plus cytarabine by defining the DLT and MTD. (Phase I) II. To determine the efficacy of the combination of Idarubicin, cytarabine and ZARNESTRA in patients with high-risk MDS and AML. (Phase II)

OUTLINE: This is a dose-escalation study of tipifarnib. Patients are stratified according to age (< 50 versus ≥ 50) and, in patients ≥ 50 years of age, cytogenetics (diploid versus unfavorable).


PHASE I: Patients receive cytarabine IV continuously on days 1-3 (or 1-4), idarubicin intravenous (IV) over 1 hour on days 1-3, and oral tipifarnib twice daily on days 1-21. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 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 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive cytarabine, idarubicin, and tipifarnib as in phase I at the MTD.

Patients in both phases who respond to induction therapy proceed to consolidation maintenance therapy.

CONSOLIDATION MAINTENANCE THERAPY: Patients receive consolidation therapy comprising cytarabine IV continuously on days 1-3, idarubicin IV over 1 hour on days 1-2, and tipifarnib twice daily on days 1-14. Treatment repeats every 4-6 weeks for 5 courses in the absence of unacceptable toxicity.

Patients then begin maintenance therapy comprising oral tipifarnib twice daily on day 1-21. Treatment repeats every 4-6 weeks for 6 courses in the absence of unacceptable toxicity.


Ages Eligible for Study:   15 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of 1) AML (WHO classification definition of > 20% blasts), or 2) high risk MDS (defined as the presence of > 10% blasts)
  • Patients must be chemo-naïve, i.e. not have received any prior chemotherapy (except hydrea) for AML or MDS; they could have received transfusions, hematopoietic growth factors or vitamins; temporary measures such as pheresis or hydrea (0.5 to 5g daily for up to 3 days) are allowed
  • ECOG PS of 0-1 at screening
  • Creatinine =< 2 mg/dl
  • Total bilirubin =< 2 mg/dL, unless increase is due to hemolysis
  • Transaminases (SGPT) =< 2.5 x ULN
  • Ability to take oral medication
  • Ability to understand and provide signed informed consent

Exclusion Criteria:

  • Subjects with APL
  • Presence of active systemic infection
  • Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results
  • Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (such as birth control pills, IUD, diaphragm, abstinence, or condoms by their partner) over the entire course of the study
  • Known allergy to imidazole drugs (such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, terconazole)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00096122

United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Jorge Cortes M.D. Anderson Cancer Center
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00096122     History of Changes
Other Study ID Numbers: NCI-2012-02862
N01CM62202 ( US NIH Grant/Contract Award Number )
Study First Received: November 9, 2004
Results First Received: June 13, 2011
Last Updated: May 9, 2014

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Neoplasm Metastasis
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Acute
Anemia, Refractory
Leukemia, Monocytic, Acute
Leukemia, Erythroblastic, Acute
Anemia, Aplastic
Anemia, Refractory, with Excess of Blasts
Leukemia, Basophilic, Acute
Leukemia, Eosinophilic, Acute
Hypereosinophilic Syndrome
Leukemia, Megakaryoblastic, Acute
Pathologic Processes
Neoplasms by Histologic Type
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplastic Processes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Eosinophilia processed this record on April 21, 2017