Activated T-Cells Expressing 2nd or 3rd Generation CD19-Specific CAR, Advanced B-Cell NHL, ALL, and CLL (SAGAN)

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.

Conditions

• Non-Hodgkin Lymphoma
• Chronic Lymphocytic Leukemia
• Acute Lymphocytic Leukemia

Interventions

GENETIC

Dose Escalation Phase:CD19.CAR/28 and CD19.CAR/28137 T cells

Three dose levels will be evaluated. Group 1: CD19.CAR/28137ζ at 1×10\^6 cells/m\^2 and CD19.CAR/28ζ at 1×10\^6 cells/m\^2 Group 2: CD19.CAR/28137ζ at 5×10\^6 cells/m\^2 and CD19.CAR/28ζ at 5×10\^6 cells/m\^2 Group 3: CD19.CAR/28137ζ at 2×10\^7 cells/m\^2 and CD19.CAR/28ζ at 2×10\^7 cells/m\^2

GENETIC

Expansion Phase: CD19.CAR/28 and CD19.CAR/28137 T cells

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.

Sponsors & Collaborators

• Center for Cell and Gene Therapy, Baylor College of Medicine

  collaborator OTHER

• The Methodist Hospital Research Institute

  collaborator OTHER

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Carlos A Ramos, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-02-28

Primary Completion

2026-12-31

Completion

2036-02-29

FDA Drug

Yes

Countries

• United States

Study Locations