Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide
Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide
This is a research study to determine the safety and effectiveness of using special cells
 that may make the subject's immune system fight their chronic lymphocytic leukemia (CLL) in
 combination with a drug called Lenalidomide.

 To do this, the investigators will put a special gene into cancer cells that have been taken
 from the subject. This will be done in the laboratory. This gene will make the cells produce
 interleukin 2 (IL-2), which is a natural substance that may help the subject's immune system
 kill cancer cells. Additionally, the investigators will stimulate the cancer cells with
 normal embryonic fibroblasts (cells that develop into normal connective tissues in the body)
 so that they will make another natural protein called CD40 ligand (CD40L). Some of these
 cells will then be put back into the subject's body with the goal that they will act like a
 vaccine and stimulate the immune system to attack the CLL cells.

 The investigators have already conducted a study similar to this in other subjects with CLL.
 In those subjects the investigators saw some changes in the subject's immune system that
 might indicate that the modified cells were helping their immune system fight the cancer.
 However, in most of the subjects this change in the immune system went away after the
 injections were stopped. The investigators think that this may be due to a high level of
 cells called T regulatory cells. T regulatory cells are part of the immune system and prevent
 excessive reactions from other cells in the body. Studies have shown that reducing T
 regulatory cells allows the body to fight the cancer for a longer period of time.

 Recent studies have shown that using Lenalidomide helps the body reduce T regulatory cells.
 Using Lenalidomide along with the injections (shots) might help the body fight the cancer for
 a longer period of time. Lenalidomide is also called Revlimid.

 In this study the investigators want to see if they can make the change in the immune system
 last longer by giving Lenalidomide before and at the same time as the vaccine. The
 investigators hope that this might produce a better response directed at the CLL cells.
 Subjects will receive injections for about a year
Previously, some of the cancer cells were taken from the subject's body and separated in the
 laboratory and a specially produced human virus (adenovirus) that carries the IL-2 gene was
 put into the cells. Adenovirus is a common virus found in human respiratory systems. In its
 normal state, it can reproduce and cause a respiratory infection. Respiratory illnesses
 caused by adenovirus infections range from the common cold to pneumonia, croup and
 bronchitis. This adenovirus has been changed in the laboratory so that it is not likely to
 reproduce or cause an infection once it is in the body. The gene transfer method used in this
 study tries to add copies of the IL2 gene that increases the immune response against a tumor.

 The rest of the cancer cells have been stimulated to express on their surface a substance
 called the human CD40L. These substances (IL-2 and CD40L), already naturally present in the
 body, are meant to help the immune system fight the cancer.

 At the point that the doctor feels the subject should begin treatment on this protocol, the
 treatment will be as follows:

 The subject will begin taking Allopurinol by mouth at 300 mg and will continue taking
 Allopurinol daily for 14 days. Allopurinol is also called Zyloprim and it will be taken to
 prevent tumor lysis syndrome. Tumor lysis syndrome can be a serious condition that occurs
 sometimes when cancer treatment is started. Tumor lysis syndrome can cause other medical
 problems.

 Two days after Allopurinol was started, the subject will begin taking Lenalidomide. The
 Lenalidomide dose will be 5 mg taken by mouth daily. The subject should swallow the capsules
 whole with water at the same time each day and should not break, chew or open the capsules.
 Females of childbearing potential who are caring for the subject should not touch the
 lenalidomide capsules or bottles without gloves. If a dose of lenalidomide is missed, it
 should be taken as soon as possible on the same day. If it is missed for the entire day, it
 should not be made up. If more than the prescribed dose is taken of lenalidomide and the
 subject feels poorly, s/he should seek emergency medical care and tell the study staff right
 away. The subject will get 1 cycle of drug per month. A max of a 28-day supply of the drug
 will be provided at one time. If the subject has bad side effects the doctor may tell him/her
 not to take the lenalidomide for a short time period or may be removed from the study.
 Otherwise, the subject will continue daily dosing with Lenalidomide for approximately 1 year,
 until four weeks after the final vaccine.

 Four weeks after the subject starts the Lenalidomide s/he will start to receive his/her
 vaccines. The vaccine will be injected under the skin (also called subcutaneously). Normally
 the subject will have the shots as an outpatient (no overnight stay in the hospital will be
 required). S/he will receive the first five (5) shots at 2 week intervals. S/he will then
 receive eleven (11) shots at 4 weekly intervals. In total, the subject may receive up to
 sixteen (16) shots over a period of one year. As with the Lenalidomide if the subject has bad
 side effects s/he may not receive his/her vaccines for a short period of time or may be
 removed from the study. Otherwise, the subject will receive the vaccines on the schedule as
 specified earlier in this paragraph. These shots must be given at Houston Methodist Hospital.

 Following these injections, the doctor will follow the subject for 1 year after the last shot
 to see how the subject is doing.

 TESTS DURING AND AFTER EXPERIMENTAL TREATMENT:

 A complete history and physical examination is necessary before the subject can be enrolled
 in the study. A physical examination will also be performed each time s/he receives a shot of
 the modified cells. The place on the subject's body where s/he had received the shots will be
 examined during the physical exam.

 Research Blood Samples:

 Blood will be taken from a tube placed into the vein (IV). We will take blood samples at the
 following time points: at study entry, week 0 when the subject starts Lenalidomide, weeks 2,
 4, 6, 8, 10 and 16 and then every 4 weeks until week 60. The last blood sample will be at one
 year after the last shot. We will do this to make sure that the Lenalidomide is working
 correctly and to study how the modified cells are working in the body.

 The amount of blood that will be obtained each time is approximately 2-3 tablespoonfuls,
 which is considered to be a safe amount. If the subject has a central line (an IV line that
 has been placed in a large blood vessel that is meant to be used for long periods of time),
 the blood will be taken from it, so that extra "sticks" should not be needed. Additional
 office visits may be necessary to obtain this blood. The maximum total amount of blood to be
 collected from the subject is 40-60 tablespoons.

 Other tests: If the subject is a woman who can get pregnant, she will have pregnancy
 counseling and urine tests as long as she is taking lenalidomide.

 In order to participate in this study, the subject must register into and follow the
 requirements of the Revlimid REMS® program of Celgene Corporation (the company that supplies
 Lenalidomide). This program provides education and counseling on the risks of fetal exposure,
 blood clots and reduced blood counts that can occur when taking Lenalidomide. The subject
 will be required to receive counseling every 28 days during treatment with lenalidomide,
 follow the pregnancy testing and birth control requirements of the program that are
 appropriate for him/her and take telephone surveys regarding your compliance with the
 program. Participating in the Revlimid REMS® program is a study requirement.
Inclusion Criteria:

 ELIGIBILITY FOR BLAST COLLECTION (procurement):

 -  Patients with B-CLL (not in Richter's transformation) with measurable disease.

 -  Procurement consent signed and faxed to Research Coordinator

 -  HIV negative (can be pending at this time)

 ELIGIBILITY FOR VACCINE AND LENALIDOMIDE ADMINISTRATION (protocol entry):

 -  Manipulated B-CLL cells available (at least 6 injections)

 -  Patients with B-CLL (not in Richter's transformation) with measurable disease

 -  Patients must have a life expectancy of at least 10 weeks.

 -  Patients must be less than 75 years old

 -  Patients must have ECOG performance status of 0-2.

 -  Patients must have recovered from the toxic effects of all prior chemotherapy before
 entering this study:

 -  Absolute neutrophil count (ANC) of greater than or equal to 500/microL

 -  Absolute lymphocyte count (ALC) greater than or equal 200/microL,

 -  Hemoglobin greater than or equal 8 g/dL

 -  Platelet count greater than or equal 50,000/microL.

 -  Patients must be willing to practice appropriate birth control methods during the
 study and for 28 days after their participation in the treatment portion of the study
 is concluded.

 -  Patients must have adequate liver function:

 -  Total bilirubin less than or equal to 1.5 mg/dl, SGOT less than or equal to 3 times
 normal

 -  Normal prothrombin time

 -  Patients must have adequate renal function (creatinine clearance greater than 50
 ml/min).

 -  Patients provide informed consent.

 -  Patient must not have received treatment with other investigational agents within the
 last 4 weeks.

 -  All study participants (treatment) must be registered in the REMS® Program and be
 willing to comply with the requirements of REMS® .

 Note: A female of childbearing potential is a sexually mature female who: 1) has not
 undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
 postmenopausal (amenorrhea following cancer therapy does not rule out childbearing
 potential) for at least 24 consecutive months (i.e., has had menses at any time in the
 preceding 24 consecutive months).

 Exclusion Criteria:

 EXCLUSION CRITERIA FOR VACCINE ADMINISTRATION (protocol entry):

 -  Infected at time of protocol entry, or receiving antibiotics (other than prophylactic
 trimethoprim sulfamethoxazole).

 -  Pregnant or lactating

 -  Suffering from an autoimmune disease (including refractory immune thrombocytopenia-ITP
 or refractory autoimmune hemolytic anemia-AIHA)

 -  Receiving immunosuppressive drugs.

 -  Received systemic steroids within 30 days of study enrollment

 -  Autologous hematopoietic stem cell transplant or fludarabine chemotherapy within 6
 months of study enrollment

 -  History of allogeneic stem cell transplant

 -  Patients with congestive heart failure or significant arrhythmia

 -  Known hypersensitivity to thalidomide or lenalidomide.