Ex Vivo-activated Autologous Lymph Node Lymphocytes in Treating Patients With Chronic Lymphocytic Leukemia

PRIMARY OBJECTIVES:

I. To assess the feasibility and safety of infusion of autologous activated T-cells (ex
vivo-activated autologous lymph node lymphocytes) in patients with chronic lymphocytic
leukemia.

SECONDARY OBJECTIVES:

I. To study immune reconstitution following infusion of activated T-cells in patients with
chronic lymphocytic leukemia.

II. To study the incidence of infections for up to 1 year following activated T cell
infusion.

III. To study the overall response rates.

OUTLINE:

Patients receive infusion of ex vivo-activated autologous lymph node lymphocytes
intravenously (IV) over 10-30 minutes on day 0.

Patients who have been previously treated on study, and subsequently need additional
infusions, may be retreated with previously cryopreserved expanded cells at the same or lower
dose level 6-12 months after the first infusion.

After completion of study treatment, patients are followed up at 1.5 years and then every 6
months for up to 5 years.

Inclusion Criteria:

- All patients must have a diagnosis of chronic lymphocytic leukemia (CLL) by
immunophenotyping and flow cytometry analysis of blood or bone marrow

- Patients must meet criteria for treatment based on the criteria proposed by
National Cancer Institute (NCI)-sponsored CLL Working Group to include at least
one of the following:

- Weight loss of more than 10% over the preceding 6 months; or

- Extreme fatigue attributable to progressive disease; or

- Fever or night sweats without evidence of infection; or

- Worsening anemia (Rai stage Ill) or thrombocytopenia (Rai stage IV); or

- Massive lymphadenopathy (> 10 cm) or rapidly progressive lymphocytosis
(lymphocyte doubling time < 6 months); or

- Prolymphocytic or Richter's transformation; or

- Patients with CLL who have received at least one prior line of therapy; or

- Patients with CLL who have frequent infections and/or recurrent secondary cancers

- No active central nervous system (CNS) disease

- All patients must have a Karnofsky performance score > 60%

- Calculated creatinine clearance (by Cockcroft-Gault) of > 50 ml/min

- Patients must not have untreated or uncontrolled life-threatening infection

- Patients must sign informed consent

Exclusion Criteria:

- Receipt of glucocorticoids (with the exception of inhaled glucocorticoid steroids for
the use of allergic rhinitis or pulmonary disease) within 2 weeks of registration

- Autoimmune disease related to CLL, e.g., idiopathic thrombocytopenic purpura (ITP) or
autoimmune hemolytic anemia, is permitted if not requiring active treatment