Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or 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: NCT00096122
Recruitment Status : Completed
First Posted : November 9, 2004
Results First Posted : July 15, 2011
Last Update Posted : May 26, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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 or disease Intervention/treatment 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

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 95 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : September 2004
Actual Primary Completion Date : September 2006
Actual Study Completion Date : February 2010

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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.

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Ages Eligible for Study:   15 Years to 70 Years   (Child, Adult, Older Adult)
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)

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): 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

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00096122     History of Changes
Other Study ID Numbers: NCI-2012-02862
N01CM62202 ( U.S. NIH Grant/Contract )
First Posted: November 9, 2004    Key Record Dates
Results First Posted: July 15, 2011
Last Update Posted: May 26, 2014
Last Verified: June 2013

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