A Phase II Study Of PS-341 (NSC 681239) In Patients With Untreated Or Relapsed Waldenstrom's Macroglobulinemia

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of Waldenstrom's macroglobulinemia confirmed by immunofixation or
immunoelectrophoresis

- Newly diagnosed or untreated with IgM ≥ 20 g/L OR

- Previously treated with IgM ≥ 5 g/L

- Non-refractory, defined as no disease progression during prior therapy or within 4
weeks of the last dose of most recent prior therapy (12 weeks for rituximab)

- Must have 1 or more of the following:

- Symptomatic lymphadenopathy

- Hepatomegaly and/or splenomegaly

- Anemia (i.e., hemoglobin < 11.0 g/dL)

- Hyperviscosity syndrome

- No other lymphoproliferative disease including transformed aggressive lymphoma

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 12 weeks

Hematopoietic

- See Disease Characteristics

- Absolute granulocyte count ≥ 1,000/mm^3

- Platelet count ≥ 50,000/mm^3

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST or ALT ≤ 2.5 times ULN

Renal

- Creatinine ≤ 1.5 times ULN

Other

- No uncontrolled bacterial, fungal, or viral infection

- No pre-existing sensory or motor neurotoxicity grade 2 or greater

- No other prior malignancy except adequately treated nonmelanoma skin cancer,
curatively treated carcinoma in situ of the cervix, or other curatively treated solid
tumor for which patient has been disease free for at least 5 years

- No other serious illness or medical condition that would preclude study participation

- No unreasonable geographical limitations

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Chemotherapy

- See Disease Characteristics

- At least 12 weeks since prior rituximab (for patients who have progressed)

- At least 24 weeks since prior rituximab (for patients who have not progressed)

- No prior high-dose chemotherapy and stem cell transplantation

- No prior radioactive monoclonal antibodies

Chemotherapy

- See Disease Characteristics

- See Biologic therapy

- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- No more than 2 prior chemotherapy regimens

- The same chemotherapy combination given for first-line and second-line therapy
is considered 2 regimens

- Single-agent rituximab not considered 1 prior regimen

- No concurrent cytotoxic chemotherapy

Endocrine therapy

- No concurrent corticosteroids

Radiotherapy

- At least 4 weeks since prior radiotherapy (except for low-dose, non- myelosuppressive
radiotherapy) and recovered

- No prior radiotherapy to more than 25% of bone marrow

Surgery

- At least 4 weeks since prior major surgery

Other

- At least 4 weeks since prior plasmapheresis

- At least 4 weeks since prior investigational anticancer therapy

- No other concurrent investigational anticancer agents or therapies