• Qualitative and quantitative toxicity [ Designated as safety issue: Yes ]
  

• Determination of immunologic efficacy [ Designated as safety issue: No ]
  
• Antitumor effects [ Designated as safety issue: No ]
  

OBJECTIVES:

• To determine the safety of autologous malignant B cells from patients with chronic lymphocytic leukemia (B-CLL), which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).
• To determine whether major histocompatability complex-restricted or unrestricted antitumor immune responses are induced by subcutaneous injections of B-CLL cells, which have been modified ex vivo to secrete hIL-2 and to express hCD40L.
• To obtain preliminary data on the antitumor effects of this treatment regimen.

OUTLINE: This is a dose-escalation study of CD40-ligand-expressing B-cell chronic lymphocytic leukemia (B-CLL) cells.

Patients undergo peripheral blood and/or leukapheresis for collection of B-CLL cells. B-CLL cells are isolated and transduced by the human interleukin-2 (IL-2) adenoviral vector and stimulated with CD40-ligand for the production of CD40-ligand-expressing and IL-2 gene-modified autologous tumor cells.

Patients receive CD40-ligand-expressing and IL-2 gene-modified autologous tumor cell vaccine subcutaneously (SC) once weekly in weeks 1, 2, and 3. Patients with stable or responding disease receive 3 additional injections on weeks 4, 6, and 8 in the absence of disease progression or unacceptable toxicity.

After a 3-4 week rest, patients are re-evaluated for toxicity and response. Patients with disease regression after the administration of 6 injections, may receive additional vaccinations once weekly at 2-week intervals.

Blood samples are collected once weekly for 10 weeks, in week 12, monthly for 1 year, and annually thereafter for 15 years for immune analysis. Samples are analyzed for immune response by numeric and phenotypical characterization of circulating leukocyte sub-populations, including analysis of CD4+, CD8+ and CD25+ T-lymphocytes, and CD16+ and CD56+ NK cells; the number of precursors reacting against autologous B-CLL cells using IFN-gamma ELISPOT assay; and the presence of immunoglobulins against autologous B-CLL cells in plasma. Tumor response is analyzed via bone marrow samples and skin punch biopsies.

After completion of study treatment, patients are followed monthly for 1 year, and then annually for 15 years.

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia

  • No Richter's transformation (e.g., aggressive non-Hodgkin lymphoma)
• Measurable or nonmeasurable disease

• Untreated patients or patients in complete remission are enrolled for vaccine administration in a therapeutic (i.e., no chemotherapy) window of three months during which the patient may not present with rapid clinical progression

  • Vaccine production for patients in complete remission can only be achieved if tumor cells have been collected before entering complete remission

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 10 weeks
• Absolute neutrophil count ≥ 500/µL
• Absolute lymphocyte count ≥ 200/μL
• Platelet count ≥ 50,000/μL
• Hemoglobin ≥ 8 g/dL
• Total bilirubin ≤ 1.5 mg/dL
• SGOT ≤ 2 times normal
• PTT normal
• Creatinine < 3 times normal for age or creatinine clearance > 80 mL/min
• No active infection
• No HIV positivity
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment

• No autoimmune disease, including any of the following:

  • Active graft-versus-host disease
  • Refractory immune thrombocytopenia
  • Refractory autoimmune hemolytic anemia

PRIOR CONCURRENT THERAPY:

• Recovered from toxic effects of all prior chemotherapy
• More than 4 weeks since prior investigational agents
• No concurrent antibiotics (except prophylactic trimethoprim sulfamethoxazole)
• No concurrent immunosuppressive drugs
• No concurrent cytotoxic therapy