Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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 Del(5q); 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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes
Intervention: tipifarnib; etoposide
Intervention description: Given orally; Given orally
Intervention MeSH terms: Etoposide; Etoposide phosphate; Tipifarnib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying the side effects and how well giving tipifarnib
      together with etoposide works in treating older patients with newly diagnosed, previously
      untreated acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking
      some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide,
      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 etoposide may kill more cancer
      cells.
    

Eligibility criteria:

        Criteria:

          -  Pathologically confirmed newly diagnosed acute myeloid leukemia (AML)

          -  Subtypes M0, M1, M2, M4-7 disease

          -  No newly diagnosed acute promyelocytic leukemia (M3)

          -  Any of the following diseases:

          -  De novo disease

          -  Secondary AML

          -  Myelodysplasia (MDS)-related AML (MDS/AML)

          -  Treatment-related AML

          -  Previously untreated disease

          -  Patients who have received prior hydroxyurea alone or non-cytotoxic therapies for MDS
             (e.g., thalidomide, interferon, cytokines, 5-azacytidine, or revlimid) will be
             eligible for this study

          -  Must be considered ineligible for traditional antileukemia chemotherapy

          -  No hyperleukocytosis with ≥ 30,000 blasts/uL or rapidly rising blast count with
             projected doubling time of =< 2 days

          -  Patients may receive hydroxyurea to lower blast count to < 30,000 blasts/uL up to 24
             hours before beginning tipifarnib and etoposide

          -  No active CNS leukemia

          -  No prior tipifarnib or etoposide

          -  No concurrent radiotherapy, immunotherapy, or other chemotherapy

          -  No concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin,
             phenobarbital, primidone, carbamazepine, or oxcarbazepine)

          -  Patients may be changed to non-enzyme-inducing anticonvulsants and stabilized before
             starting study treatment

        Inclusion Criteria:

          -  ECOG performance status 0-2

          -  Serum creatinine =< 2.0 mg/dL

          -  SGOT and SGPT =< 3 times upper limit of normal

          -  Bilirubin =< 2 mg/dL

        Exclusion Criteria:

          -  Active, uncontrolled infection

          -  Patients with infection under active treatment and controlled with antimicrobials are
             eligible

          -  Presence of other life-threatening illnesses

          -  Patients with mental deficits and/or psychiatric history that preclude them from
             giving informed consent or from following protocol

          -  Allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, or econazole)