Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia
Condition: 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
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Neoplasm Metastasis; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Anemia; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Hypereosinophilic Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      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).

      INDUCTION THERAPY:

      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.
    

Intervention name(s): cytarabine; idarubicin; tipifarnib
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Given IV; Given IV; Given orally
Other intervention name(s): ARA-C; arabinofuranosylcytosine; arabinosylcytosine; Cytosar-U; cytosine arabinoside; 4-demethoxydaunorubicin; 4-DMDR; DMDR; IDA; R115777; Zarnestra
Intervention MeSH terms: Cytarabine; Idarubicin; Tipifarnib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment