Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide

• Status: Terminated
• Trial end date: 2015-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; The Methodist Hospital Research Institute; The Methodist Hospital System
• Treatments: Lenalidomide; Thalidomide; Vaccines

Criteria

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.