Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen

Summary

Patients eligible for this study have a type of blood cancer called T-cell leukemia or lymphoma (lymph gland cancer).

The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research combines two different ways of fighting disease, antibodies and T cells. Antibodies are proteins that protect the body from bacterial and other diseases. T cells, or T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and T cells have shown promise treating patients with cancers, but have not been strong enough to cure most patients.

T lymphocytes can kill tumor cells but there normally are not enough of them. Some researchers have taken T cells from a person's blood, grown more in the lab then given them back to the person. In some patients who've had recent bone marrow or stem cell transplant, the number of T cells in their blood may not be enough to grow in the lab. In this case, T cells may be collected from their previous transplant donor, who has a similar tissue type.

The antibody used in this study, called anti-CD5, first came from mice that have developed immunity to human leukemia. This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD5. CD5 antibodies have been used to treat people with T-cell leukemia and lymphoma. For this study, anti-CD5 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 lab, investigators have also found that T cells work better if stimulating proteins, such as one called CD28, are also added. Adding the CD28 makes the cells grow better and last longer in the body, giving them a better chance of killing the leukemia or lymphoma cells.

In this study investigators will attach the CD5 chimeric receptor with CD28 added to it to the patient's T cells or the previous bone marrow transplant donor's T cells. The investigators will then test how long the cells last. The decision to use the bone marrow transplant donor's T cells instead of the patient's will be based on 1) whether there is an available and willing donor and 2) the likelihood of the patient's T cells being able to grow in the lab. These CD5 chimeric receptor T cells with CD28 are investigational products not approved by the FDA.

UPDATE: Please note that the Autologous Arm of this study is now closed.

Conditions

• T-cell Acute Lymphoblastic Lymphoma
• T-non-Hodgkin Lymphoma
• T-cell Acute Lymphoblastic Leukemia

Interventions

GENETIC

Autologous CD5.CAR/28zeta CAR T cells

Three dose levels will be evaluated: Dose level one: 1×10\^7 cells/m2 Dose level two: 5×10\^7 cells/m2 Dose level three: 1×10\^8 cells/m2

GENETIC

Allogeneic CD5.CAR/28zeta CAR T cells

Three dose levels will be evaluated: Dose level one: 1×10\^7 cells/m2 Dose level two: 5×10\^7 cells/m2 Dose level three: 1×10\^8 cells/m2

Sponsors & Collaborators

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

  collaborator OTHER

• The Methodist Hospital Research Institute

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• Baylor College of Medicine

  lead OTHER

Principal Investigators

• Rayne Rouce, 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

2017-11-01

Primary Completion

2028-06-01

Completion

2040-09-01

FDA Drug

Yes

Countries

• United States

Study Locations