A Study of Gleevec in Patients With Idiopathic Myelofibrosis or Chronic Myelomonocytic Leukemia (CMML)

Gleevec will be administered at a dose of 400 mg orally once daily.

Patients will continue to receive the drug until either drug progression or the development of intolerable side effects.

Patients will be assessed with a complete blood count weekly for the first 8 weeks and will have monthly physical examinations and bone marrow examinations every 3 months.

Inclusion criteria

• Patients must have a clinical diagnosis of myelofibrosis with myeloid metaplasia or chronic myelomonocytic leukemia (CMML). Patients may be entered based on a prior cytogenetic karyotype showing the absence of the Philadelphia chromosome.
• Patients may be entered prior to completion of reverse transcription-polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization (FISH) studies, but a patient who is subsequently found to be BCR-ABL or FISH positive will be removed from protocol treatment. FISH will only be performed on patients with a normal karyotype. A PCR sample will be sent on all patients.
• The patients with myelodysplasia must have French-American-British (FAB) subtype chronic myelomonocytic leukemia (CMML) defined as peripheral blood monocytosis, and less than 30 percent blasts in the peripheral blood or the bone marrow.
• The patients with myelofibrosis with myeloid metaplasia can have one of the following: agnogenic myeloid metaplasia (idiopathic myelofibrosis), or post-polycythemic myeloid metaplasia (post-polycythemic myelofibrosis), or post-thrombocythemic myeloid metaplasia.
• Estimated life expectancy of 6 months or greater.
• Serum bilirubin equal to or less than twice the upper limit of normal.
• Serum SGOT and SGPT equal to or less than twice the upper limit of normal.
• Serum creatinine equal to or less than twice the upper limit of normal.
• Age at least 18 years.
• Greater than 4 weeks from any chemotherapy (except hydroxyurea), radiotherapy, immunotherapy, or systemic glucocorticoid therapy (non-glucocorticoid hormonal therapy is allowed). Systemic glucocorticoid therapy for non-malignant disease is allowed.
• The last dose of hydroxyurea must be 24 hours prior to the initiation of Gleevec.
• Greater than 2 months following bone marrow or peripheral blood stem cell transplantation or treatment with donor lymphocyte infusion (DLI).

Exclusion criteria

• Uncontrolled active infection.
• Pregnancy or nursing mothers.
• Patients with myelofibrosis with myeloid metaplasia or chronic myelomonocytic leukemia who have transformed to acute myelogenous leukemia.
• Prior treatment or diagnosis of acute myelogenous leukemia.
• Patients with Philadelphia positive cytogenetics by either peripheral blood or bone marrow sampling.
• Eastern Cooperative Oncology Group (ECOG) performance status > 3.
• Prior exposure to Gleevec.
• Active central nervous system (CNS) disease.
• Evidence of infection with the human immunodeficiency virus.
• Active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely.