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)

Recruiting now · Phase 1

Conditions studied: 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

In brief

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.

Key facts

Study ID: NCT07055477
Run by: National Cancer Institute (NCI)
People needed: 60
Starts: 2025-09-29
Expected to finish: 2044-06-01
Last updated by the study team: 2026-07-17

Who can join

Age: 18 and older, up to 120. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Participants with any current or prior CNS involvement by malignancy are excluded from this study. All potential participants will be screened with brain imaging prior to enrollment on study.
Participants with >1000 atypical cells/mm\^3 by peripheral blood flow cytometry at screening.
Participants with a history of serologically or biopsy confirmed autoimmune disorders are excluded from this study. As an exception, participants with EATL whose celiac disease is well controlled and who will maintain a strict gluten-free diet are eligible.
Participants with prior autoimmune thyroiditis who are now on stable thyroid replacement therapy are also eligible.
HTLV I/II positive participants with a history of HTLV-associated myelopathy/tropical spastic paraparesis (TSP)
Participants who have received prior CD25-directed therapy.
Current or prior anti-cancer treatment prior to the first dose of study drug as defined below:
Any cytotoxic therapy, immunotherapy, antitumor vaccines or monoclonal antibodies within 2 weeks before the start of lymphodepleting chemotherapy.
High doses of systemic corticosteroids (>20 mg prednisone or equivalent) 5 days before apheresis and/or 5 days before CAR T cell infusion.
Participants who have not reached D+100 following auto-SCT or who have any unresolved Auto-SCT related complications (e.g. pneumonitis).
Participants who have undergone prior allogeneic stem cell at any time.
Participants taking any investigational agents for any disease/ condition.
Seropositive for human immunodeficiency virus (HIV).
Active bacterial infections or active viral infections (CMV, syphilis)
Uncontrolled EBV infection Note: EBV positive test is allowed due to frequent association of active EBV with mature T-cell malignancies, which frequently resolve with improved control of the malignancy. EBV positive participants may be treated with rituximab or biosimilar prior to lymphodepleting chemotherapy at investigator s discretion.
Active hepatitis C infection.
NOTE: Participants seropositive for hepatitis C virus (HCV) infection must have been treated and cured as defined by undetectable HCV viral load.
Active hepatitis B infection.
NOTE: Participants that are positive for hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) must have a negative hepatitis B virus polymerase chain reaction (HBV PCR) result <100 IU/mL at screening. Those who are HBV PCR positive are excluded. Those hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with a negative PCR for hepatitis B will be treated with antivirals designed to prevent hepatitis B reactivation (e.g., entecavir) and have monitoring for hepatitis B reactivation with PCR.
Participants with current cardiac atrial or cardiac ventricular lymphoma involvement.
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months of enrollment.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computer tomography (CT) scan at screening.
NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
History or presence of non-malignant CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
Deep vein thrombosis or pulmonary embolism requiring ongoing systemic anticoagulation

Where it is running

National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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