Clinical trial NCT01853631: Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)
Official title: Phase I Study of Activated T-Cells Expressing Second or Third Generation CD19-Specific Chimeric Antigen Receptors for Advanced B-Cell Non-Hodgkin's Lymphoma, Acute Lymphocytic Leukemia and Chronic Lymphocytic Leukemia (SAGAN)
Conditions: Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Acute Lymphocytic Leukemia
Summary: Subjects on this study have a type of lymph gland cancer called Non-Hodgkin Lymphoma, acute lymphocytic leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "lymphoma" or "leukemia"). The lymphoma or leukemia has come back or has not gone away after treatment.
The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Both antibodies and T cells have been used to treat patients with cancer. They have shown promise, but have not been strong enough to cure most patients.
T cells can kill tumor cells but normally there are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person.
The antibody used in this study is called anti-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, anti-CD19 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor.
In the laboratory, the investigators found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells last longer in the body but not long enough for them to be able to kill the lymphoma cells. The investigators believe that if they add an extra stimulating protein, called CD137, the cells will have a better chance of killing the lymphoma cells.
The investigators are going to see if this is true by putting the CD19 chimeric receptor with CD28 alone into half of the cells and the CD19 chimeric receptor with CD28 and CD137 into the other half of the cells. These CD19 chimeric receptor T cells with CD28 and with or without CD137 are investigational products not approved by the FDA.
The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how long the T cell with each sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.
Interventions:
description: Three dose levels will be evaluated.<br/>Group 1: CD19.CAR/28137ζ at 1×10^6 cells/m^2 and CD19.CAR/28ζ at 1×10^6 cells/m^2<br/>Group 2: CD19.CAR/28137ζ at 5×10^6 cells/m^2 and CD19.CAR/28ζ at 5×10^6 cells/m^2<br/>Group 3: CD19.CAR/28137ζ at 2×10^7 cells/m^2 and CD19.CAR/28ζ at 2×10^7 cells/m^2
name: Dose Escalation Phase:CD19.CAR/28 and CD19.CAR/28137 T cells
type: Genetic
description: The primary goal of the expanded cohort is to further study the safety profiles of CAR-T cells in each of the disease settings, both with or without lymphodepleting chemotherapy given before CAR-T cell infusion.
name: Expansion Phase: CD19.CAR/28 and CD19.CAR/28137 T cells
type: Genetic
Study arms:
design_group_description: Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.
design_group_title: Dose Escalation: CD19 CAR T Cells for B-cell ALL
design_group_type: Experimental
design_group_description: Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.
design_group_title: Dose Expansion: CD19 CAR T Cells for B-cell ALL
design_group_type: Experimental
design_group_description: Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.
design_group_title: Dose Escalation: CD19 CAR T Cells for B-cell NHL/CLL
design_group_type: Experimental
design_group_description: Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.
design_group_title: Dose Expansion: CD19 CAR T Cells for B-cell NHL/CLL
design_group_type: Experimental
Sponsor: Baylor College of Medicine
Collaborators: Center For Cell & Gene Therapy
The Methodist Hospital Research Institute
Drug name mappings:
name: Virus-specific-CD19.CAR(Baylor College of Medicine)
lang: EN