The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD138 antigen (CAR138 T cells).
In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying the patient's genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes a piece of an antibody called anti-CD138. This antibody floats around in the blood and can detect and stick to cancer cells called multiple myeloma cells because they have a substance on the outside of the cells called CD138. Anti-CD138 antibodies have been used to treat people with multiple myeloma, but have not been strong enough to cure most patients. For this study, the anti-CD138 antibody has been changed so that instead of floating free in the blood part of it is now joined to the T cells. Only the part of the antibody that sticks to the multiple myeloma cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD138 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.
Cell Procurement Up to 300 mL total of peripheral blood (up to 3 collections) will be obtained from patients for cell procurement. In patients with a low CD3 count in the peripheral blood (less than 200/μl by flow cytometry), a leukopheresis may be performed to isolate sufficient T-cells. The parameters for pheresis will be 2 blood volumes.
CAR138 T-cell Administration Autologous CAR138 T-cells will be administered 2-4 days following lymphodepletion. The lymphodepletion regimen will consist of Cyclophosphamide 1.5 g/m2 IV as a single infusion over 2 hours. Mesna will also be administered for prevention of hemorrhagic cystitis (300mg/m2 IV infused over 30 minutes, 15 minutes prior to starting cyclophosphamide + 600mg/m2 by mouth 2 hours after the cyclophosphamide infusion is complete + 600mg/m2 by mouth 6 hours after the cyclophosphamide infusion is complete).
Duration of Therapy Autologous CAR138 T-cells will be administered 2-14 days following lymphodepletion with cyclophosphamide and fludarabine by a licensed provider (oncology registered nurse or physician) via intravenous injection over 5-10 minutes through either a peripheral or central line. The expected volume is 1-50cc.
Treatment with one infusion will be administered unless:
The first 3 patients enrolled in the study will receive 5x10^6 CAR138 T-cells/m^2 via infusion. The number of cells for the infusion will be increased to 1x10^7 CAR138 T-cells/m^2 and then, 2.5x10^7 CAR138 T-cells/m^2, 5x10^7 CAR138 T-cells/m^2, 1x10^8 CAR138 T-cells/m^2 and 2x10^8 CAR138 T-cells/m^2 in subsequent cohorts of 3 patients provided no dose limiting toxicities (DLTs) are observed within 4 weeks of the cell infusion. Cohort enrollment will be staggered, requiring each patient to complete at least 2 weeks of safety monitoring following CAR138 T-cell infusion at the designated dose level for the cohort before another patient is allowed to enroll in the cohort.
Duration of Follow-up Patients will be followed for up to 15 years for replication-competent retrovirus evaluation or until death, whichever occurs first. Patients removed from study for unacceptable adverse events will continue follow up for evaluation of progression free survival, overall survival and replication-competent retrovirus monitoring.
Patients who experience disease progression after receiving a cell infusion will still be required to complete abbreviated follow up procedures.
The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.
The following criteria is provided for health care professionals.
The following is a listing of trial locations that are open and accepting patients.
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