Bortezomib in Treating Patients With Advanced Myeloproliferative Disorders

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced myeloproliferative disorder, including 1 of the following subtypes:

  • Myelofibrosis with myeloid metaplasia defined by the following criteria:

    • Evaluable or symptomatic disease as evidenced by ≥ 1 of the following:

      • Anemia, defined as hemoglobin \< 10 g/dL OR erythrocyte-transfusion dependence, defined as requiring 1 transfusion within the past 8 weeks
      • Symptomatic palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) requiring treatment* NOTE: *Subjective but painful enough to mandate intervention

  • Chronic myelomonocytic leukemia (CMML) defined by the following criteria:

    • Absence of an imatinib mesylate-sensitive molecular abnormality for CMML (i.e., t[5;12], t[5;10], t[1;5], and t[5;7]) confirmed by fluorescent in situ hybridization (FISH) or standard cytogenetic bone marrow analysis within the past 18 months

    • Symptomatic disease as evidenced by ≥ 1 of the following:

      • Anemia, defined as hemoglobin \< 10 g/dL OR erythrocyte-transfusion dependence, defined as requiring 1 transfusion within the past 8 weeks
      • Palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) requiring treatment* NOTE: *Subjective but painful enough to mandate intervention
      • Leukocytosis associated with ascites, serositis, pleural effusions, vasculitis, or other overt manifestation

  • Systemic mast cell disease defined by the following criteria:

    • Absence of the FIP1LI-PDGFRA mutation as confirmed by FISH
    • Evaluable and symptomatic disease requiring therapy, as evidenced by involvement with organs other than skin (i.e., heart, bowel, peripheral blood, liver/spleen, or marrow)
    • Debilitating mast cell mediator symptoms not responsive to standard therapy such as antihistamines
• Absence of t(9;22) translocation as confirmed by FISH or standard cytogenetic peripheral blood or marrow analysis at any prior time point

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Not incarcerated in a municipal, county, state, or federal prison
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³
• Creatinine ≤ 2.0 mg/dL
• Total or direct bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 3 times upper limit of normal (unless clinically attributed to hepatic extramedullary hematopoiesis)
• No baseline peripheral or autonomic neuropathy ≥ grade 2
• No other condition or laboratory abnormality that would place the patient at unacceptable risk or confound the ability to interpret study data
• No hypersensitivity to boron, mannitol, or bortezomib
• No myocardial infarction within the past 6 months
• No New York Hospital Association class III-IV heart failure
• No uncontrolled angina
• No severe uncontrolled ventricular arrhythmia

• No evidence of acute ischemia or active conduction system abnormality by ECG

  • ECG screening abnormalities must be documented as not medically relevant
• No other serious medical or psychiatric illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

• At least 14 days since prior chemotherapy (e.g., interferon alfa, anagrelide, or other myelosuppressive agent) or any other experimental therapy
• At least 14 days since prior growth factors
• At least 14 days since prior systemic use of corticosteroids
• More than 14 days since prior investigational drugs
• Concurrent hydroxyurea allowed for ≤ 14 days during study therapy if clinically indicated for extreme leukocytosis control