Actively Recruiting
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)
Led by National Cancer Institute (NCI) · Updated on 2026-02-20
60
Participants Needed
1
Research Sites
974 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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
Official Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Confirmed diagnosis of relapsed or refractory CCR4-positive mature T-cell lymphoma including specific subtypes such as PTCL-NOS, AITL, ALCL, HSTCL, MEITL, EATL, CTCL (including mycosis fungoides and subacute panniculitis-like T-cell lymphoma), or lymphomatous ATL without CNS involvement or significant circulating disease
- CCR4 positivity defined as 10% or more malignant cells expressing CCR4 by immunohistochemistry
- Availability of adequate tissue samples from biopsy for CCR4 testing
- Relapsed or refractory disease after prior therapies: at least one prior Brentuximab-containing therapy for ALCL, all standard therapies exhausted for mycosis fungoides, and at least two prior therapies for other subtypes
- Measurable or evaluable disease on CT, PET, or mSWAT criteria
- Age 18 years or older
- ECOG performance status 0 or 1
- Adequate organ function including neutrophil count ≥ 1,000/µL, platelets ≥ 75,000/µL, hemoglobin ≥ 9 g/dL, creatinine clearance ≥ 60 mL/min/1.73m², bilirubin ≤ 3 times upper limit of normal, AST and ALT ≤ 3 times upper limit of normal, left ventricular ejection fraction > 50%, normal ECG without significant arrhythmias
- Lung function with FEV1 and DLCO > 60% predicted
- Negative pregnancy test for individuals of child-bearing potential
- Agreement to use effective contraception during and after study treatment
- Willingness to discontinue nursing through 12 weeks after cell infusion
- Ability and willingness to stay within one-hour drive from clinical center for follow-up visits through month 3
- Ability to understand and sign informed consent
You will not qualify if you...
- Current or prior central nervous system involvement by lymphoma
- Peripheral blood atypical cells >1000/mm³ by flow cytometry
- History of autoimmune disorders (except controlled celiac disease or stable autoimmune thyroiditis)
- HTLV I/II positive with related neurological disease
- Prior CD25-directed therapy
- Recent cytotoxic therapy, immunotherapy, vaccines, or monoclonal antibodies within 2 weeks before lymphodepleting chemotherapy
- High-dose systemic corticosteroids within 5 days before leukapheresis or CAR T cell infusion
- Less than 100 days post-autologous stem cell transplant or unresolved transplant complications
- Prior allogeneic stem cell transplant
- Use of investigational agents for any condition
- HIV positive
- Active bacterial or viral infections (except controlled EBV)
- Active hepatitis C infection without cure
- Active hepatitis B infection with detectable viral load
- Cardiac lymphoma involvement or recent significant cardiac disease
- History of severe lung diseases or active pneumonitis
- Non-malignant CNS disorders including seizures or autoimmune CNS disease
- Current deep vein thrombosis or pulmonary embolism requiring anticoagulation
- Severe allergy to tocilizumab or study agents
- Other malignancies requiring treatment within past 3 years except certain skin cancers
- Uncontrolled intercurrent illnesses that could increase risk or affect study results
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
N
NCI Medical Oncology Referral Office
CONTACT
S
Samuel Y Ng, M.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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