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