Tipifarnib in Treating Patients With Myeloproliferative Disorders

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia (CML)

  • Philadelphia chromosome (Ph) positive OR
  • BCR-ABL positive by polymerase chain reaction

  • Must meet 1 of the following 2 conditions:

    • Chronic phase

      • Persistent or progressive disease on maximum tolerated interferon or imatinib mesylate, as evidenced by increasing WBC count, peripheral blood myeloid immaturity, progressive anemia, and/or persistence or relapse of abnormal cytogenetics and/or molecular findings
      • Interferon or imatinib mesylate intolerant

    • Accelerated phase

      • Persistent or progressive disease on imatinib mesylate
    • Patients who have not received interferon or imatinib mesylate due to allergy or refusal are eligible OR

• Diagnosis of chronic myelomonocytic leukemia

  • Proliferative type (WBC at least 12,000/mm3)
  • Less than 5% blasts in peripheral blood and no more than 20% blasts in bone marrow OR
• Diagnosis of undifferentiated myeloproliferative disorder OR
• Diagnosis of atypical CML (Ph negative)

• No blast crisis phase of CML, atypical CML, or undifferentiated myeloproliferative disorders

  • No more than 20% blasts in peripheral blood or bone marrow
• Diagnosed more than 3 months before study entry

PATIENT CHARACTERISTICS:

Age:

• 21 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 4 months

Hematopoietic:

• See Disease Characteristics
• No requirement for platelet transfusion
• No thrombocytopenia-related bleeding

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST/ALT no greater than 2 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Capable of swallowing capsules
• No other concurrent severe disease that would preclude study compliance
• No septicemia or other severe infection

• No iron deficiency

  • If marrow aspirate not available, transferrin saturation at least 20% and ferritin greater than 50 ng/mL
• No other contributing causes of anemia (e.g., autoimmune or hereditary hemolytic disorders, gastrointestinal blood loss, B12 or folate deficiency, or hypothyroidism)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• At least 4 weeks since prior interferon
• At least 4 weeks since prior hematopoietic growth factors
• No prior allogeneic bone marrow transplantation

Chemotherapy:

• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) except for hydroxyurea which may be used to manage elevated cell counts through the beginning of the second course of study therapy

Endocrine therapy:

• No concurrent androgens
• No concurrent corticosteroids (e.g., greater than 10 mg/day prednisone or equivalent steroid dosage) except as premedication for transfusions

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• No other concurrent standard or investigational cytotoxic agents