Trials / Recruiting

RecruitingNCT07055477

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)

A Phase I Trial of 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)

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 60 (estimated)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years – 120 Years
Healthy volunteers: Not accepted

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.

Detailed description

Background: * Chemokine receptor 4 (CCR4) the receptor for C-C chemokines CCL17 \[Thymus and activation-regulated chemokine (TARC)\] and CCL22 \[Macrophage-derived chemokine (MDC)\] is expressed on some subsets of normal human T lymphocytes including T regulatory cells (Tregs), TH2 and TH17 cells. It is also widely expressed in mature T-cell malignancies. * The anti-CCR4 antibody, mogamulizumab, has shown appreciable clinical activity against CCR4 expressing T-cell malignancies suggesting this molecule to be a robust therapeutic target. * A lentivirus vector-based 2nd generation anti-CCR4 chimeric antigen receptor (CCR4-CAR.4-1BB-CD3Zeta) has been generated, and its functionality and specificity have been validated in in-vitro cell lysis assays with several patient-derived CCR4+ malignant T cells lines as has its efficacy in a murine xenograft preclinical model of ATL. Objectives: -Determine safety of administering autologous CCR4 CAR T cells. Eligibility: * Diagnosis of relapsed/refractory mature T cell malignancy that expresses CCR4 including: 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 Tcell lymphoma (CTCL) including mycosis fungoides and subacute panniculitis-like Tcell Lymphoma or lymphomatous subtypes of ATL without evidence of CNS involvement or substantial circulating disease. * Age \>=18 years. * Adequate organ function and absence of medical conditions that would preclude safe administration of this treatment. Design: * Single-institution, open-label, non-randomized, 3+3 pilot dose escalation trial * Participants will undergo leukapheresis to obtain T-cells that will be genetically modified to express anti-CCR4 CARs on T-cells. Groups of 3 to 6 participants will receive autologous CCR4 CAR T cells at doses of 0.3 x 10\^6/kg, 1 x 10\^6/kg and 3 x 10\^6/kg provided that DLT has not been reached; If the first dose level exceeds the MTD, a subsequent cohort of 3-6 participants will be treated at the dose level of 0.1 x 10\^6/kg. * Up to 9 additional participants will be treated at the MTD or the maximum administered dose to better assess the activity of this treatment regimen. * Participants will be monitored for toxicity, antitumor effects and persistence of CCR4 CAR T-cells and assessed for response with periodic re-staging imaging and laboratory testing. * Statistical analyses will be limited to summary statistics by dose level and for all participants for safety parameters, biologic effects, response rate and survival.

Conditions

Interventions

Type	Name	Description
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

Timeline

Start date: 2025-09-29
Primary completion: 2044-06-01
Completion: 2044-06-01
First posted: 2025-07-09
Last updated: 2026-02-20

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT07055477. Inclusion in this directory is not an endorsement.