A Phase II Pilot Study of VELCADE in Patients With MDS

Inclusion Criteria

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