Treatment of B-CLL With Human IL-2 and CD40 Ligand and Plasmid Gene Modified Autologous Tumor Cells

This is a phase I trial to assess the safety of a dose escalation of hCD40L-expressing autologous tumor cells with a fixed dose of recombinant hIL-2 gene transduced autologous leukemic blasts. All eligible patients will be treated with a minimum of three and up to six injections. There will be no use of placebo or control subjects.

Inclusion criteria

• Patients are eligible for administration of their vaccine if they present with B-CLL (not in Richters transformation) with (group A) or without (group B) (Inclusion of B-CLL) measurable disease. Untreated or complete remission patients will be enrolled for vaccine administration in a therapeutic (i.e., no chemotherapy) window of three months. If during these three months (necessary to complete the vaccine study), the patient presents with rapid clinical progression, he or she will be excluded from our current study and will receive treatment according to the standard institutional guidelines. IMPORTANT NOTE: vaccine production for complete remission patients can only be achieved if tumor cells have been collected BEFORE entering complete remission.
• Patients must have a life expectancy of at least 10 weeks.
• Patients must have ECOG performance status of 0-2 as below: 0 = up and about, no restriction, 1 = Ambulatory, no strenuous activity, 2 = Ambulatory, capable of self-care appropriate for age. Up and about > 50% of time, but unable to carry out any physical activities or attend school, 3 = Limited self-care only. Up and about < 50% of time, 4 = Disabled, no self care. Bedridden or confined to chair.
• Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and must have an absolute neutrophil count (ANC) of > / = 500/mL, absolute lymphocyte count (ALC) > / = 200/mL, hemoglobin > / = 8g/dL, and platelet count > / = 50,000/mL
• Patients must not be infected at time of protocol entry, and should not be receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole).
• Patients must be HIV-negative.
• Patients must be willing to practice appropriate birth control methods during the study and for 3 months after the study is concluded. This includes total abstinence, oral contraceptives, an intrauterine device, contraceptive implants under the skin, contraceptive injections (Depo-Provera). Contraceptive foam with a condom is allowed. The male partner should use a condom.
• Patients must not be suffering from an autoimmune disease (including active graft-versus-host disease-GvHD, refractory immune thrombocytopenia-ITP or refractory autoimmune hemolytic anemia-AIHA) and should not be receiving immunosuppressive drugs.
• Patients must have adequate liver function (total bilirubin < / = 1.5mg/dl, SGOT < / = 2 times normal, normal prothrombin time).
• Patients must have adequate renal function (creatinine less than 3 times normal for age or creatinine clearance > 80mg/min/1.73m2).
• Patients must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side-effects. Patients will be given a copy of the consent form.
• Patient must not have received treatment with other investigational agents within the last 4 weeks.

Exclusion criteria

• Richters transformation (aggressive non-Hodgkins lymphoma),
• active infection,
• significant autoimmune disease (including active GvHD, ITP and AIHA),
• requirement for immunosuppressive drugs,
• inadequate liver and/or renal function,
• pregnancy or lactation,
• refusal to practice birth control methods,
• seropositive for HIV,
• life expectancy less than 10 weeks