A Phase II Study of Gleevec (Imatinib Mesylate) In Patients With BCR-Negative Myeloproliferative Disorders Including Patients With Idiopathic Myelofibrosis With Myeloid Dysplasia or Chronic Myelomonocytic Leukemia
- 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
- 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).
- 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
- 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