A Phase I Trial Anti-CC Chemokine Receptor 4 Chimeric Antigen Receptor T Cells (CCR4 CAR T Cells) for CCR4 Expressing T-cell Malignancies Including Peripheral T-cell Non-Hodgkin Lymphoma (PTCL) and Cutaneous T-cell Non-Hodgkin Lymphoma (CTCL)

Summary

Background:

Chemokine receptor 4 (CCR4) is a protein that is found on the surface of certain T-cell lymphoma cells and is common in mature T-cell cancers. White blood cells can be changed with molecules called anti-CCR4 to express a chimeric antigen receptors (CAR), which is a molecule that directs a white blood cell to attack other cells. The CAR in this study attacks the CCR4 protein found on your T-cell lymphoma. This type if therapy is called gene therapy. Gene therapy involves a person s own white blood cells modified to target cancer cells. More research is needed to find out if gene therapy can treat T-cell cancers and do it safely.

Objective:

To test safety of giving people with certain mature T-cell lymphomas their own white blood cells modified with anti-CCR-4 CAR.

Eligibility:

People aged 18 and older with certain mature T-cell lymphomas that have not responded to or have come back after treatment. They must have a T-cell lymphoma that has CCR4 on the surface of the cancer cells.

Design:

Participants will be screened. They will have a medical history and physical exam. Tests of blood, urine, and heart and lung function will be done.

Participants will have tests:

Computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging scans: They will lie on a table that slides into a donut-shaped machine or a tube. Pictures of the inside of the body will be taken. Before the PET scan, they will get an injection of radioactive fluid in a vein in the arm. Before the MRI, they may get a contrast dye injected through a vein (IV) in the arm.

A biopsy of the tumor may be taken. A bone marrow sample may be taken from the hip: The area will be numbed and a large needle inserted through the skin.

Leukapheresis will be done to obtain T-cells that will be genetically modified to express anti-CCR4 CARs on T-cells: Blood is drawn through an IV in one arm, circulated through a machine, and then returned through an IV in the other arm.

Chemotherapy drugs will be given in an IV to prepare the body to accept the modified CAR T cells.

The modified cells will be given in an IV.

Participants will be followed for 15 years: This will require blood tests over the first 1-2 years followed by yearly visits and possibly telehealth updates.

Conditions

• Relapsed and/or Refractory Mature T Cell Malignancy
• Peripheral T-Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Anaplastic Large Cell Lymphoma
• Hepatosplenic T-cell Lymphoma
• Monomorphic Epithelialtropic Intestinal Lymphoma
• Enteropathy Associated T-cell Lymphoma
• Cutaneous T-Cell Lymphoma
• Mycosis Fungoides
• Subacute Panniculitis-like T-cell Lymphoma

Interventions

DRUG

Cyclophosphamide

Days -5 to -3: Cyclophosphamide 300 mg/m\^2 x 3 days

DRUG

Fludarabine

Days -5 to -3: Fludarabine 30 mg/m\^2 IV daily over 30 minutes for 3 days

BIOLOGICAL

Autologous CCR4 CAR T cells

Day 0: Cells will be infused intravenously (IV) over 10-30 minutes

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Samuel Y Ng, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-29

Primary Completion

2044-06-01

Completion

2044-06-01

FDA Drug

Yes

Countries

• United States

Study Locations