Phase II Study of a Proteasome Inhibitor, PS-341 (NSC 681239) in Chronic Myelogenous Leukemia (CML) in Chronic or Accelerated Phase

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML)
in chronic or accelerated phase, defined as having any of the following:

- Peripheral blood (PB) or bone marrow (BM) blasts at least 10% but less than 30%

- PB or BM blasts and promyelocytes at least 20%

- PB or BM basophils at least 20%

- Progressive splenomegaly (at least 10 cm confirmed twice at least 4 weeks apart
or 50% increase in splenomegaly over 4 weeks)

- Clonal evolution defined as the presence of additional cytogenetic abnormalities
other than the Ph chromosome

- Thrombocytopenia (platelet count less than 100,000/mm^3) unrelated to therapy

- Hemoglobin less than 7 g/dL unrelated to therapy or bleeding

- Failed prior treatment with imatinib mesylate or intolerant, unable, or unwilling to
receive it

- Ineligible for higher-priority or higher-efficacy regimens or protocols

- No blastic phase CML

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy:

- At least 18 weeks

Hematopoietic:

- See Disease Characteristics

Hepatic:

- Bilirubin no greater than 1.5 mg/dL

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Creatinine clearance greater than 60 mL/min

Other:

- No other concurrent illness that would preclude study entry

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- No more than 2 prior cytotoxic regimens in addition to imatinib mesylate and/or
hydroxyurea

- At least 4 weeks since prior chemotherapy and recovered

- Concurrent hydroxyurea and/or anagrelide allowed during first 2 courses

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 4 weeks since prior radiotherapy and recovered

Surgery:

- Not specified

Other:

- See Disease Characteristics

- See Chemotherapy

- At least 24 hours since prior imatinib mesylate

- No other concurrent investigational agents