Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL

Summary

The body has different ways of fighting infection and disease. No single way is 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 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 with bacteria or viruses. 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 treat cancer. This study will combine both T cells and antibodies in order to create a more effective treatment called Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen (ATLCAR.CD30). Another treatment being tested includes the Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen with CCR4 (ATLCAR.CD30.CCR4) to help the cells move to regions in the patient's body where the cancer is present. Participants in this study will receive either ATLCAR.CD30.CCR4 cells alone or will receive ATLCAR.CD30.CCR4 cells combined with ATLCAR.CD30 cells.

Previous studies have shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so 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. These CD30 chimeric (combination) receptor-activated T cells (ATLCAR.CD30) can 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.

Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy tumor cells. T cells naturally produce a protein called CCR4 which functions as a navigation system directing T cells toward tumor cells specifically. In this study, researchers will also genetically modify ATLCAR.CD30 cells to produce more CCR4 proteins and they will be called ATLCAR.CD30.CCR4. The study team believes that the ATLCAR.CD30.CCR4 cells will be guided directly toward the tumor cells based on their navigation system. In addition, the study team believes the majority of ATLCAR.CD30 cells will also be guided directly toward tumor cells when given together with ATLCAR.CD30.CCR4, increasing their anti-cancer fighting ability.

This is the first time ATLCAR\>CD30.CCR4 cells or combination of ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells are used to treat lymphoma. The purpose of this study to determine the following:

* What is the safe dose of ATLCAR.CD30.CCR4 cells to give to patients
* What is the safe dose of the combination of ATLCAR.CD30 and ATLCAR.CD30.CCR4 cells to give to patients

Conditions

• Lymphoma
• Immune System Diseases
• Immunoproliferative Disorders
• Lymphatic Diseases
• Lymphoproliferative Disorders
• Neoplasms
• Cutaneous Lymphoma
• Cutaneous Anaplastic Large Cell Lymphoma
• Mycosis Fungoides
• Sezary Syndrome
• Lymphomatoid Papulosis
• Cutaneous T Cell Lymphoma
• Gray Zone Lymphoma

Interventions

BIOLOGICAL

ATLCAR.CD30.CCR4 cells

Three dose levels are being evaluated: 2x10\^7, 5x10\^7, 1x10\^8

BIOLOGICAL

ALTCAR.CD30 cells

Fixed dose level of 1x10\^8

DRUG

Bendamustine

70 mg/m\^2/day Bendamustine for 3 days for lymphodepletion prior to cell infusion

DRUG

Fludarabine

30 mg/m\^2/day Fludarabine for 3 days for lymphodepletion prior to cell infusion

Sponsors & Collaborators

• Stand Up To Cancer

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• UNC Lineberger Comprehensive Cancer Center

  lead OTHER

Principal Investigators

• Natalie Grover, MD · UNC Lineberger Comprehensive Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-12-12

Primary Completion

2025-12-16

Completion

2039-11-04

FDA Drug

Yes

Countries

• United States

Study Locations