Phase I/II Study of G3139 (Genasense) in Patients With Waldenstrom's Macroglobulinemia

Inclusion Criteria:

- Diagnosis of Waldenstrom's macroglobulinemia (WM) confirmed by both of the
following:

- Bone marrow lymphoplasmacytosis with greater than 10% lymphoplasmacytic cells or
aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on
bone marrow biopsy

- Measurable disease, defined by quantitative IgM monoclonal protein greater than
1,000 mg/dL

- Symptomatic relapsed or refractory disease requiring therapy, defined by at least 1
of the following:

- Impaired bone marrow function due to disease infiltration as demonstrated by
any of the following:

- Hemoglobin less than 11 g/dL

- Requires epoetin alfa therapy to maintain hemoglobin of at least 11 g/dL

- Platelet count less than 100,000/mm^3

- Symptomatic bulky lymphadenopathy

- Symptoms attributable to hyperviscosity (e.g., nose bleeding, gingival bleeding,
or retinal hemorrhage) or serum viscosity level relative to water greater than 4

- Received at least 1 prior chemotherapy regimen which included chlorambucil,
cyclophosphamide, fludarabine, cladribine, or pentostatin

- No secondary leukemia or history of antecedent hematologic disorder (e.g.,
myelodysplasia) prior to initial onset of WM

- Performance status - ECOG 0-2

- Not specified

- See Disease Characteristics

- Absolute neutrophil count at least 1,000/mm^3*

- Platelet count at least 50,000/mm^3*

- No bleeding disorder

- Bilirubin no greater than 2 times upper limit of normal (ULN)

- AST less than 1.5 times ULN

- Albumin at least 2.5 g/dL

- PT no greater than 1.5 times ULN

- INR no greater than 1.3

- PTT no greater than 1.5 times ULN

- No history of chronic hepatitis or cirrhosis

- Creatinine no greater than 2 times ULN

- No uncontrolled congestive heart failure

- No active symptoms of coronary artery disease, including the following:

- Uncontrolled arrhythmias

- Recurrent chest pain despite prophylactic medication

- No New York Heart Association class III or IV heart disease

- No grade 2 or greater cardiovascular signs and symptoms within the past 4 weeks

- HIV negative

- Direct Coombs' test negative

- No autoimmune thrombocytopenia

- No uncontrolled serious infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Adequate venous access for 7-day continuous infusion of study drug

- Intellectual, emotional, and physical ability to maintain an ambulatory infusion pump

- No other cancer except adequately treated basal cell or squamous cell skin cancer,
carcinoma in situ of the cervix, or other cancer from which the patient has been
disease-free for at least 5 years

- No known hypersensitivity to phosphorothioate-containing oligonucleotides

- No uncontrolled seizure disorder

- More than 21 days since prior immunotherapy for WM

- More than 21 days since prior cytokine, biologic, or vaccine therapy for WM

- More than 8 weeks since prior plasmapheresis or plasma exchange

- No prior allogeneic stem cell transplantation

- No concurrent plasmapheresis or plasma exchange

- See Disease Characteristics

- No concurrent corticosteroid therapy

- More than 21 days since prior radiotherapy for WM

- More than 21 days since prior major surgery for WM

- No prior organ allograft

- Recovered from all prior therapy

- More than 21 days since other prior therapy for WM

- No other concurrent investigational therapy

- No concurrent immunosuppressive drugs

- No concurrent therapeutic anticoagulation therapy