Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of relapsed or refractory chronic lymphocytic leukemia (CLL) requiring
therapy

- Primary resistance, defined as disease progression without response during at
least 2 courses of myelosuppressive therapy OR

- Relapsed disease, defined as a response (remission or plateau) followed by
relapse on or off prior therapy

- At least 1 prior regimen must have contained fludarabine

- Intermediate or high-risk CLL

- Intermediate-risk disease must satisfy at least 1 of the following criteria for
active disease:

- Massive or progressive splenomegaly and/or lymphadenopathy

- Spleen tip greater than 6 cm below costal margin

- More than 10% weight loss within the past 6 months

- Grade 2 or 3 fatigue

- Fevers greater than 100.5 degrees F or night sweats for more than 2 weeks
without evidence of infection

- Progressive lymphocytosis with an increase of more than 50% over a 2-month
period or an anticipated doubling time of less than 6 months

- Worsening anemia or thrombocytopenia

- Measurable disease with all of the following:

- Absolute lymphocytosis greater than 5,000/mm^3

- Lymphocytosis of small to moderate-size lymphocytes with less than 55%
prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically determined
by manual differential

- Bone marrow aspirate smear with at least 30% nucleated cells that are lymphoid
or a bone marrow core biopsy showing lymphoid infiltrates compatible with CLL

- Normocellular or hypercellular bone marrow

- Lymphocyte immunophenotype that shows a predominant B-cell monoclonal population

- No Rai stage 0 CLL or stable CLL not requiring therapy

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

PATIENT CHARACTERISTICS:

Age:

- Over 18

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

- Platelet count at least 50,000/mm^3 (hematopoietic growth factor or transfusion
independent)

- Negative Coombs' test

- No bleeding or coagulation disorder

- No history of hemolytic anemia, including autoimmune hemolytic anemia

- No history of autoimmune thrombocytopenia

Hepatic:

- Albumin at least 3.0 g/dL

- Bilirubin no greater than 2 mg/dL

- AST no greater than 1.5 times upper limit of normal (ULN) (5 times ULN if due to CLL)

- PT no greater than 1.5 times ULN OR

- INR no greater than 1.3

- PTT no greater than 1.5 times ULN

- No chronic hepatitis or cirrhosis

Renal:

- Creatinine no greater than 2.0 mg/dL

Cardiovascular:

- No uncontrolled congestive heart failure

- No active symptoms of coronary artery disease (i.e., uncontrolled arrhythmia or
recurrent chest pain despite prophylactic medication)

- No New York Heart Association class III or IV disease

- No cardiovascular signs or symptoms grade 2 or greater

Other:

- Able to maintain an ambulatory infusion pump

- HIV negative

- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix

- No known hypersensitivity to phosphorothioate-containing oligonucleotides,
fludarabine, or cyclophosphamide

- No concurrent medical disease that would preclude study participation

- No uncontrolled seizure disorder

- No unresolved serious infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior autologous or allogeneic stem cell transplantation

- At least 3 weeks since prior immunologic therapy, cytokine therapy, vaccine therapy,
or other biologic therapy for CLL and recovered

- No concurrent interleukin-11

Chemotherapy:

- See Disease Characteristics

- At least 3 weeks since prior chemotherapy and recovered

Endocrine therapy:

- No concurrent corticosteroid therapy

Radiotherapy:

- At least 3 weeks since prior radiotherapy for CLL and recovered

Surgery:

- No prior organ allograft

- At least 3 weeks since prior major surgery for CLL and recovered

Other:

- At least 3 weeks since other prior therapy for CLL and recovered

- No other concurrent investigational therapy

- No concurrent therapeutic anticoagulation

- No concurrent immunosuppressive drugs