A Lymphodepleting Combination of Total Body Irradiation and Cyclophosphamide before CAR T-Cell Therapy (Cilta-Cel) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Poor Kidney Function
This phase I trial tests the safety and side effects of a lymphodepleting combination of total body irradiation (TBI) and cyclophosphamide before chimeric antigen receptor (CAR) T-cell (T) therapy (cilta-cel) for the treatment of patients with multiple myeloma that has come back after a period of improvement (relapsed) or multiple myeloma that has not responded to previous treatment (refractory) and poor kidney function. CAR T therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. In order to receive CAR T therapy, patients must first undergo lymphodepleting chemotherapy, which is a combination of chemotherapy drugs with the purpose of preparing the body so that the CAR T therapy is able to kill cancer cells. However, the standard lymphodepleting combination of two chemotherapy drugs is not able to be given to patients with poor kidney function. Patients with poor kidney function are able to receive one of the standard lymphodepletion chemotherapy drugs, cyclophosphamide. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s DNA and may kill cancer cells. It may also lower the body’s immune response. In place of the other standard lymphodepletion chemotherapy drug that patients with poor kidney function cannot receive, this trial will use TBI. TBI is radiation to the whole body using high energy x-rays or particles to kill cancer cells. Giving a lymphodepleting combination of TBI and cyclophosphamide before CAR T therapy may be safe and tolerable for the treatment of patients with relapsed or refractory multiple myeloma and poor kidney function.