RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase II trial to study the effectiveness of tipifarnib in treating patients who have myelofibrosis with myeloid metaplasia.

OBJECTIVES:

• Determine the response rate in patients with myelofibrosis with myeloid metaplasia treated with tipifarnib.
• Determine the toxicity of this drug in these patients.
• Determine the effect of this drug on disease-associated anemia, palpable splenomegaly, and hypercatabolic symptoms in these patients.
• Determine the effect of this drug on the pathologic increase in circulating myeloid progenitors from baseline to after the first course in these patients.
• Correlate response/relapse in these patients with in vitro myeloid colony sensitivity to this drug.
• Determine the effect of this drug on bone marrow histologic features (osteosclerosis, reticulin fibrosis, and angiogenesis) in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 2 years.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 15 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed myelofibrosis with myeloid metaplasia

  • Agnogenic myeloid metaplasia
  • Post-polycythemic myeloid metaplasia
  • Post-thrombocythemic myeloid metaplasia
• Bone marrow must show reticulin fibrosis and peripheral blood smear must show leukoerythroblastosis and dacrocytosis

• Bone marrow must not show evidence of other conditions associated with myelofibrosis, including the following:

  • Metastatic carcinoma
  • Lymphoma
  • Myelodysplasia
  • Hairy cell leukemia
  • Mast cell disease
  • Acute leukemia (including M7 type)
  • Acute myelofibrosis
• Absence of chromosomal translocation t(9:22) by bone marrow chromosome analysis or peripheral blood or bone marrow fluorescent in situ hybridization (FISH)

• At least 1 of the following must be present:

  • Anemia evidenced by hemoglobin less than 10 g/dL
  • Palpable hepatosplenomegaly

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 750/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 3 times ULN (unless secondary to disease)

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent uncontrolled illness or comorbid condition that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• No known quinolone sensitivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent epoetin alfa
• No concurrent prophylactic colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
• No concurrent thalidomide

Chemotherapy

• More than 2 weeks since prior cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 2 weeks since prior myelosuppressive agents
• No other concurrent therapy directed at the disease