Fludarabine and Cyclophosphamide With or Without Oblimersen in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

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