Low-Dose Decitabine in Treating Patients With Symptomatic Myelofibrosis

OBJECTIVES:

- Determine the efficacy and safety of low-dose decitabine in patients with symptomatic
primary myelofibrosis (PMF) or post essential thrombocythemic (ET) or polycythemic vera
(PV) myelofibrosis.

- Analyze the ability of this drug to decrease pathologic angiogenesis and other stromal
reactive features intrinsic to PMF or post ET/PV myelofibrosis.

OUTLINE: Patients receive low-dose decitabine IV over 1 hour on days 1-5. Treatment repeats
every 28 days for up to 6 courses in the absence of disease progression or unacceptable
toxicity. Patients achieving partial remission, complete remission, or clinical improvement
may receive up to 12 courses of decitabine in the absence of disease progression or
unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 3 years.

DISEASE CHARACTERISTICS:

- Histological confirmation of primary myelofibrosis or post essential thrombocythemic
or polycythemic vera myelofibrosis

- Reticulin fibrosis ≥ grade 1

- Evaluable and symptomatic disease worthy of treatment, characterized by ≥ 1 of the
following:

- Anemia, defined as hemoglobin < 11 g/dL or erythrocyte transfusion dependence

- Palpable and symptomatic splenomegaly (palpable and symptomatic hepatomegaly is
acceptable if previously splenectomized)

- Severe, disease-related constitutional symptoms, including ≥ 1 of the following:

- Severe night sweats

- Fevers

- Weight loss

- Bone pain

- Absence of t(9;22) by fluorescent in situ hybridization (FISH) or standard
cytogenetics OR prior demonstration of a lack of this translocation

PATIENT CHARACTERISTICS:

- Eastern Co-operative Oncology Group (ECOG) performance status 0-3

- Absolute neutrophil count (ANC) ≥ 1,000/mm³

- Platelet count ≥ 50,000/mm³

- Creatinine ≤ 2.0 mg/dL

- Direct or total bilirubin ≤ 2.0 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times upper
limit of normal (ULN) (≤ 5 times ULN if elevation is attributed to hepatic
extramedullary hematopoiesis)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Not incarcerated in a municipality, county, state, or federal prison

- No serious medical condition or psychiatric illness that would preclude signing the
informed consent

- No condition that, in the opinion of the treating physician, places the patient at
unacceptable risk for study participation or confounds the ability to interpret study
data

- Able to adhere to the study visit schedule and other study requirements

PRIOR CONCURRENT THERAPY:

- No other concurrent chemotherapy (e.g., hydroxyurea, thalidomide, interferon alpha,
anagrelide, or other myelosuppressive agent) or experimental therapy