CCR4 CAR T Cells for T-cell Lymphoma
This study is testing a new gene therapy called Autologous CCR4 CAR T cells for people with certain types of relapsed or refractory (meaning it came back or didn't respond to previous treatment) T-cell lymphoma. This therapy uses your own white blood cells, which are specially modified to target a protein called CCR4 found on your cancer cells. Before receiving the CCR4 CAR T cells, you will receive two chemotherapy drugs, Cyclophosphamide and Fludarabine. The main goal of this study is to see how safe this new treatment is. You may be able to join if you are an adult with a confirmed diagnosis of CCR4-positive T-cell lymphoma, such as Peripheral T-cell Lymphoma (PTCL) or Angioimmunoblastic T-cell Lymphoma (AITL). The study plans to enroll 60 participants.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It aims to enroll 60 participants.
- What's involved
- You will receive Cyclophosphamide and Fludarabine chemotherapy for three days, followed by an intravenous infusion of Autologous CCR4 CAR T cells.
- Compensation
- Not stated in the trial record.
- Follow-up
- The safety of the treatment will be determined at 12 weeks after receiving the CCR4 CAR T cells.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07055477
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
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~60 participants
Updated 2026-08-24 on ClinicalTrials.gov
What's tested:CyclophosphamideFludarabineAutologous CCR4 CAR T cells
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Determine safety profile of administering autologous CCR4 CAR T cells
Measured over 12 weeks
Conditions
NCT07055477
Where you'd take part
This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
National Institutes of Health Clinical Center
Bethesda, Marylandstudy coordinator listed
Recruiting
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Samuel Y Ng, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Eligibility criteria
Inclusion
Pathologically (biopsy) confirmed histologic diagnosis of a relapsed/refractory CCR4+ mature T-cell malignancy from one of the following subtypes: peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), hepatosplenic t-cell lymphoma (HSTCL), monomorphic epithelialtropic intestinal lymphoma (MEITL), enteropathy associated T-cell lymphoma (EATL) or cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and subacute panniculitis-like T-cell Lymphoma, or lymphomatous subtypes of ATL without evidence of CNS involvement or substantial circulating disease confirmed by the Laboratory of Pathology, NCI.
CCR4+ is defined as \>= 10% malignant cells positive for CCR4 by immunohistochemistry. It is preferred to have a fresh biopsy to confirm the CCR4 status. In the event a fresh biopsy cannot be safely performed in the opinion of the treating physician, an archival biopsy sample taken at the time of previous progression can be used.
Adequate tissue \[a formalin fixed tissue block or 15 slides of tumor sample (archival or fresh)\] from diagnostic biopsy (archival or fresh) must be available.
Participants must have disease that is relapsed or refractory after prior therapy as follows:
Participants with ALCL must have failed at least one prior line of Brentuximab-containing therapy.
Due to the generally indolent nature of the disease, participants with Mycosis Fungoides must have exhausted all standard therapies as determined by the enrolling physician and principal investigator to be eligible for this study.
All other participants must have failed at least two lines of prior therapy.
Participants must have measurable or evaluable disease at the time of enrollment. For participants with systemic T-cell lymphoma, this is defined by any evidence from CT scan or PET-CT-avid disease based on the Lugano criteria. For participants with Cutaneous T-cell Lymphoma, positive scores based on Modified Severity-Weighted Assessment Tool (mSWAT) criteria are acceptable.
Participants must be \>=18 years of age at the time of signing informed consent.
Adequate performance status (PS) as follows: ECOG PS 0-1.
Adequate organ function as evidenced by the following laboratory parameters:
Absolute neutrophil count (ANC) \>= 1,000 /microL
Platelets \>= 75,000 / microL
Hemoglobin (Hgb) \>= 9 g/dL (transfusions permitted)
Creatinine Clearance \>= 60 mL/min/1.73m\^2 per Cockcroft Gault equation; For participants \< 60 per Cockcroft Gault a direct measurement may be used
Serum total bilirubin \<= 3 X upper limit of normal (ULN)
Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) \<= 3 X ULN
Left ventricular ejection fraction \> 50% by echocardiogram performed
ECG No clinically significant ECG findings (Arrhythmias or evidence of ischemic heart disease with clinical correlate)
FEV1 and DLCO \> 60% of predicted (adjustment for Hgb acceptable)
Individuals of child-bearing potential (IOCBP) must have a negative urine or blood HCG pregnancy test at screening.
Individuals of child-bearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD\], abstinence, surgical sterilization) or practice abstinence starting at the time of study entry, for the duration of study therapy, and 12 months after the last dose of combined chemotherapy.
Nursing participants must be willing to discontinue nursing through 12 weeks after cell infusion.
Potential participants must agree to stay within 1-hour drive of NIH clinical center from date of initial discharge from hospitalization (no earlier than D+15) through initial D+28 follow-up and be willing and able to return for in-person follow-up visits through month 3 of the study.
Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
Exclusion
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.
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.
Active hepatitis B infection.
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.
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
History of severe immediate hypersensitivity reaction to tocilizumab or any of the agents used in this study
Participants with second malignancies in addition to their T-cell malignancy are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the participant.
What this trial measures
- Determine safety profile of administering autologous CCR4 CAR T cells12 weeks
The number of participants who experience Adverse Events per CTCAE v5.0, by type, grade and frequency of toxicities from time of lymphodepleting regimen through 12 weeks after the last cell infusion.