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)

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Conditions

Relapsed and/or Refractory Mature T Cell MalignancyPeripheral T-Cell LymphomaAngioimmunoblastic T-cell LymphomaAnaplastic Large Cell LymphomaHepatosplenic T-cell LymphomaMonomorphic Epithelialtropic Intestinal LymphomaEnteropathy Associated T-cell LymphomaCutaneous T-Cell LymphomaMycosis FungoidesSubacute Panniculitis-like T-cell LymphomaCCR4CAR TChemokine Receptor 4Chimeric Antigen ReceptorGene TherapyCell TherapyImmunotherapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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....

Official Title

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)

Quick Facts

Study Start:2025-09-03
Study Completion:2044-06-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT07055477

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * 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.
  2. * 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.
  3. * Participants must have disease that is relapsed or refractory after prior therapy as follows:
  4. * Participants with ALCL must have failed at least one prior line of Brentuximab-containing therapy.
  5. * 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.
  6. * All other participants must have failed at least two lines of prior therapy.
  7. * Participants must have measurable or evaluable disease at the time of enrollment, defined by any evidence from CT scan and PET-CT-avid disease based on the Lugano criteria.
  8. * Participants must be \>=18 years of age at the time of signing informed consent.
  9. * Adequate performance status (PS) as follows: ECOG PS 0-1.
  10. * Adequate organ function as evidenced by the following laboratory parameters:
  11. * Absolute neutrophil count (ANC) \>= 1,000 /microL
  12. * Platelets \>= 75,000 / microL
  13. * Hemoglobin (Hgb) \>= 9 g/dL (transfusions permitted)
  14. * Creatinine Clearance \>= 60 mL/min/1.73m\^2 per Cockcroft Gault equation; For participants \< 60 per Cockcroft Gault a direct measurement may be used
  15. * Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) \<= 3 X ULN
  16. * Left ventricular ejection fraction \> 50% by echocardiogram performed
  17. * ECG No clinically significant ECG findings (Arrhythmias or evidence of ischemic heart disease with clinical correlate)
  18. * Nursing participants must be willing to discontinue nursing through 12 weeks after cell infusion.
  19. * 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.
  20. * Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
  1. * 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.
  2. * Participants with \>1000 atypical cells/dL by peripheral blood flow cytometry at screening.
  3. * 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.
  4. * HTLV I/II positive participants with a history of HTLV-associated myelopathy/tropical spastic paraparesis (TSP)
  5. * Participants who have received prior CD25-directed therapy.
  6. * Current or prior anti-cancer treatment prior to the first dose of study drug as defined below:
  7. * Any cytotoxic therapy, immunotherapy, antitumor vaccines or monoclonal antibodies within 2 weeks before the start of lymphodepleting chemotherapy.
  8. * High doses of systemic corticosteroids (\>20 mg prednisone or equivalent) 5 days before apheresis and/or 5 days before CAR T cell infusion.
  9. * Participants who have not reached D+100 following auto-SCT or who have any unresolved Auto-SCT related complications (e.g. pneumonitis).
  10. * Participants who have undergone prior allogeneic stem cell at any time.
  11. * Participants taking any investigational agents for any disease/ condition.
  12. * Seropositive for human immunodeficiency virus (HIV).
  13. * Active bacterial infections or active viral infections (CMV, syphilis)
  14. * 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.
  15. * Active hepatitis C infection.
  16. * Participants with current cardiac atrial or cardiac ventricular lymphoma involvement.
  17. * 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.
  18. * 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.
  19. * 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
  20. * Deep vein thrombosis or pulmonary embolism requiring ongoing systemic anticoagulation
  21. * History of severe immediate hypersensitivity reaction to tocilizumab or any of the agents used in this study
  22. * 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.
  23. * Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the participant.

Contacts and Locations

Study Contact

NCI Medical Oncology Referral Office
CONTACT
(240) 760-6050
ncimo_referrals@nih.gov
Samuel Y Ng, M.D.
CONTACT
(240) 858-7618
samuel.ng@nih.gov

Principal Investigator

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

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-09-03
Study Completion Date2044-06-01

Study Record Updates

Study Start Date2025-09-03
Study Completion Date2044-06-01

Terms related to this study

Keywords Provided by Researchers

  • CCR4
  • CAR T
  • Chemokine Receptor 4
  • Chimeric Antigen Receptor
  • Gene Therapy
  • Cell Therapy
  • Immunotherapy

Additional Relevant MeSH Terms

  • 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