azacitidine in treating patients with myelofibrosis

Conditions: Chronic Myeloproliferative Disorders; Secondary Myelofibrosis

Summary: rationale: drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. purpose: this phase ii trial is studying how well azacitidine works in treating patients with myelofibrosis.

objectives: primary * determine the efficacy of azacitidine in patients with myelofibrosis (mf) with myeloid metaplasia. * evaluate the safety of azacitidine in these patients. secondary * evaluate pertinent biologic characteristics of mf before and during therapy with azacitidine. * assess the effects of study treatment on constitutional symptoms in these patients. * estimate time to event distributions for overall survival and progression. outline: patients receive azacitidine subcutaneously once daily on days 1-5. treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. after completion of study treatment, patients are followed periodically for up to 3 years. projected accrual: a total of 35 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed myelofibrosis with myeloid metaplasia (mmm), including any of the following subtypes: * agnogenic myeloid metaplasia * post-polycythemic myeloid metaplasia * post-thrombocythemic myeloid metaplasia * evaluable and symptomatic disease, defined as 1 of the following: * anemia (hemoglobin \< 10 g/dl or erythrocyte transfusion-dependent, requiring 1 transfusion ≤ 8 weeks) * treatment required\* for symptomatic palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) note: \*subjective but painful enough to mandate intervention * absence of t(9;22) by fluorescent in situ hybridization (fish) or standard cytogenetics (by peripheral blood or marrow) - previous demonstration of a lack of this translocation (at any point) is sufficient * no advanced malignant hepatic tumors patient characteristics: * ecog performance status 0-2 * absolute neutrophil count ≥ 1,000/mm³ * platelet count ≥ 50,000/mm³ * creatinine ≤ 2.0 mg/dl * total bilirubin ≤ 2.0 mg/dl or direct bilirubin ≤ 2.0 mg/dl if total bilirubin elevated (unless attributed to underlying disease) * ast and alt ≤ 2 times upper limit of normal (unless clinically attributed to hepatic extramedullary hematopoiesis) * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no baseline peripheral or autonomic neuropathy ≥ grade 2 * no condition, including the presence of laboratory abnormalities, that would preclude study compliance * no hypersensitivity to mannitol or azacitidine * not incarcerated in a municipality (i.e., county, state, or federal prison) prior concurrent therapy: * at least 14 days since prior chemotherapy, including interferon alfa, anagrelide, or other myelosuppressive agents * at least 14 days since prior systemic corticosteroids * at least 14 days since prior investigational agents

Keywords: primary myelofibrosis polycythemia vera essential thrombocythemia secondary myelofibrosis