Decitabine in Treating Patients With Myelofibrosis
Condition: Primary Myelofibrosis; Secondary Myelofibrosis
MeSH terms: Primary Myelofibrosis
Intervention: Decitabine; Laboratory Biomarker Analysis
Intervention description: Given SC; Correlative studies
Intervention MeSH terms: Decitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well decitabine works in treating
      patients with myelofibrosis, a cancer of the blood system associated with fibrosis (scar
      tissue) in the bone marrow that is advanced and for which there is no standard therapy.
      Decitabine may block the actions of some proteins that are responsible for turning certain
      genes off in various cancers including myelofibrosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed myeloid metaplasia with
             myelofibrosis (this includes all subtypes - chronic idiopathic myelofibrosis or
             angiogenic myeloid metaplasia, post thrombocythemic and post polycythemic
             myelofibrosis); patients must have anemia (hemoglobin < 11 g/dL) or palpable
             splenomegaly (measured in cm from costal margin - to be eligible); patients with
             palpable splenomegaly must have spleen size documented ultrasonographically as well;
             they must also meet standard diagnostic criteria for MMM

          -  Patients with morphologic evidence of advanced phases of the disease including
             accelerated (10-19% blasts) phase or with evidence of evolution to acute leukemia (>=
             20% blasts) are also eligible for this study

          -  The Italian Diagnostic Criteria for MMM

               -  Necessary criteria

                    -  Diffuse bone marrow fibrosis

                    -  Absence of the Philadelphia chromosome or BCR-ABL rearrangement in
                       peripheral blood cells

               -  Optional criteria

                    -  Splenomegaly of any grade

                    -  Anisopoikilocytosis with tear drop erythrocytes

                    -  Presence of circulating immature myeloid cells

                    -  Presence of circulating erythroblasts

                    -  Presence of clusters of megakaryoblasts and anomalous megakaryocytes in bone
                       marrow sections

                    -  Myeloid metaplasia

               -  Diagnosis of MMM is acceptable if the following combinations are present

                    -  The two necessary criteria plus any other two optional criteria when
                       splenomegaly is present OR

                    -  The two necessary criteria plus any other four optional criteria when
                       splenomegaly is absent

          -  Patients may have had prior chemotherapy or radiation therapy including splenic
             irradiation; prior therapy with erythropoietin, granulocyte-colony stimulating factor
             (GCSF), other growth factors or androgenic steroids is also permitted; there is no
             limit to the number of prior regimens received; at least 4 weeks must have elapsed
             since prior chemo or radiation therapy; at least 2 weeks must have elapsed since
             growth factor (erythropoietin, GCSF, granulocyte-macrophage colony-stimulating factor
             [GM-CSF]) or other therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Total bilirubin =< 2mg/dL

               -  In patients with associated hemolytic anemia; total bilirubin > 2mg/dL is
                  permissible as long as this is as a result of predominantly unconjugated
                  hyperbilirubinemia; such patients may be enrolled only after discussion with the
                  study chair

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 3 x institutional upper limit of normal unless due to disease

          -  Serum creatinine =< 2mg/dL

          -  Patients must not be pregnant or nursing; women of child- bearing potential and men
             must agree to use an effective contraceptive method; should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Prior therapy with decitabine

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients with known central nervous system (CNS) disease should be excluded from this
             clinical trial

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to decitabine

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with decitabine

          -  Human immunodeficiency virus (HIV)-positive patients receiving combination
             anti-retroviral therapy are excluded from the study