Bortezomib in Treating Patients With Myelodysplastic Syndromes

DISEASE CHARACTERISTICS:

• Diagnosis of myelodysplastic syndromes (MDS)

• Requires treatment or transfusion support for MDS, as indicated by 1 of the following:

  • Demonstrates transfusion or epoetin alfa dependence

    • Transfusion dependence is defined as requiring ≥ 2 units of packed RBCs within an 8-week period prior to study entry

  • Hemoglobin < 11g/dL on 2 separate occasions 2 weeks apart

    • No iron, cyanocobalamin (vitamin B_12), or folic acid deficiency or other causes of anemia

• Must have 1 of the following FAB subtypes:

  • Refractory anemia
  • Refractory anemia with ringed sideroblasts
  • Refractory anemia with excess blasts
  • Secondary MDS (if ≥ 3 years since active primary cancer)
• No chronic myelomonocytic leukemia
• Not refractory to platelet transfusion support (i.e., inability to maintain platelet count > 20,000/mm^3 with transfusion)
• No current acute myelogenous leukemia (e.g., > 30% blasts)

PATIENT CHARACTERISTICS:

Performance status

• Karnofsky 50-100%

Life expectancy

• At least 6 months

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin ≤ 2 mg/dL
• AST and ALT < 2 times upper limit of normal

Renal

• Creatinine clearance ≥ 30 mL/min

Cardiovascular

• No significant cardiovascular condition that would preclude study participation
• No uncontrolled hypertension

Pulmonary

• No significant pulmonary condition that would preclude study participation

Immunologic

• No serious concurrent infection

  • Active infections must be adequately treated with antibiotics prior to study entry
• No hypersensitivity to bortezomib, boron, or mannitol

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for up to 4 weeks after completion of study treatment
• No peripheral neuropathy ≥ grade 2
• No uncontrolled seizure activity, as defined by no activity within the past year on stable anticonvulsant medications
• No other malignancy within the past 3 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No endocrine, neurologic, or other systemic disease that would preclude study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior allogeneic bone marrow transplantation
• Concurrent transfusion support allowed
• Concurrent epoetin alfa or darbepoetin alfa allowed if initiated before start of study therapy, dose is stable for ≥ 4 weeks, and dose is stable during study participation
• No concurrent platelet growth factor support
• No concurrent thalidomide

Chemotherapy

• No concurrent chemotherapy
• No concurrent hydroxyurea

Endocrine therapy

• Concurrent corticosteroids for chronic autoimmune or inflammatory condition allowed if initiated before start of study therapy and maintained on a stable or decreasing dose

Other

• Recovered from all prior therapies
• At least 4 weeks since prior MDS therapy, except epoetin alfa, darbepoetin alfa, filgrastim (G-CSF), pegfilgrastim (G-CSF), or transfusion support
• At least 30 days since prior investigational agents
• No prior bortezomib
• No other concurrent investigational agents
• No other concurrent therapy for MDS