CCR4 CAR T Cells for T-Cell Lymphoma

Overseen By Samuel Y Ng, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Investigational agents

Disqualifiers: CNS involvement, Autoimmune disorders, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety of a new gene therapy for certain mature T-cell lymphomas that haven't responded to other treatments. The therapy, called Autologous CCR4 CAR T cells, uses a patient's own white blood cells, modified to attack cancer cells with a specific protein called CCR4. People with T-cell lymphomas that have the CCR4 protein and who haven't seen success with previous treatments might be a good fit for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take any investigational agents or certain cancer treatments close to the start of the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that CAR T cells, including the CCR4 CAR T cells under study, have been used safely in other types of cancer. In previous studies with similar treatments, many patients experienced positive outcomes. However, some side effects, such as fever and low blood pressure, were reported and are common with this kind of therapy.

The treatment involves modifying a person's own white blood cells to help fight cancer. This approach has successfully treated some cancers that did not respond to other treatments. As a Phase 1 trial, this study primarily focuses on testing the treatment's safety. Researchers are still learning about its tolerability and potential side effects. Participants will receive close monitoring throughout the trial to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about autologous CCR4 CAR T cells for T-cell lymphoma because this treatment offers a novel approach by genetically modifying a patient's own immune cells to specifically target and destroy cancer cells expressing the CCR4 protein. Unlike traditional chemotherapy or radiation, which can harm both healthy and cancerous cells, this CAR T-cell therapy aims to provide a more precise attack on the lymphoma cells, potentially reducing side effects and improving effectiveness. Additionally, this treatment involves escalating doses and determining the maximum tolerated dose, which could optimize the balance between efficacy and safety.

What evidence suggests that this treatment might be an effective treatment for T-cell lymphoma?

Research has shown that a new treatment using CCR4 CAR T cells could be promising for T-cell lymphomas, a type of cancer. In this trial, participants will receive conditioning chemotherapy with cyclophosphamide and fludarabine, followed by autologous CCR4 CAR T-cells. These specially modified white blood cells can find and attack cancer cells with the CCR4 protein. In past studies, 40% to 74% of patients with similar cancers experienced complete remission. This treatment harnesses the body's own immune system, reprogramming its cells to target the cancer, which is why researchers remain hopeful about its potential. ^{3 6 7 8 9}

Who Is on the Research Team?

Samuel Y Ng, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for adults with certain mature T-cell lymphomas that express CCR4 and have not improved or returned after treatment. Participants must be over 18, have a specific type of T-cell lymphoma, and undergo screening tests including blood, urine, heart and lung function tests.

Inclusion Criteria

* 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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis and Cell Modification

Leukapheresis is performed to obtain T-cells, which are then genetically modified to express anti-CCR4 CARs

2-3 weeks

1 visit (in-person)

Conditioning Chemotherapy

Participants receive conditioning chemotherapy with cyclophosphamide and fludarabine to prepare the body for CAR T-cell infusion

1 week

1 visit (in-person)

CAR T-cell Infusion

Infusion of autologous CCR4 CAR T-cells at escalating doses

1 day

1 visit (in-person)

Initial Monitoring

Participants are monitored for toxicity, antitumor effects, and persistence of CCR4 CAR T-cells

12 weeks

Periodic visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with periodic imaging and laboratory testing

15 years

Yearly visits (in-person and telehealth)

What Are the Treatments Tested in This Trial?

Interventions

• Autologous CCR4 CAR T cells

Trial Overview The study is testing the safety of gene therapy using patients' own white blood cells modified to target cancer cells with anti-CCR4 CAR (chimeric antigen receptors). It involves leukapheresis to collect T-cells, chemotherapy preparation, then infusion of the engineered CAR T-cells.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 3 Interventions

Conditioning chemotherapy with cyclophosphamide and fludarabine followed by autologous CCR4 CAR T-cells (IV) at the MTD

Group II: Arm 1 Experimental Treatment 3 Interventions

Conditioning chemotherapy with cyclophosphamide and fludarabine followed by autologous CCR4 CAR T-cells (IV) at escalating doses

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10345856/

Identifying highly active anti-CCR4 CAR T cells for the ... In summary, CCR4–depleted anti-CCR4 CAR T cells are enriched in Th1 and CD8+ T cells and exhibit high antitumor efficacy against CCR4–expressing T-cell ...

2. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy In the multicentre trials that followed, complete response (CR) rates of 40–54%, 67% and 69–74% were observed in patients with R/R aggressive B ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924007432

CAR T-cell therapies for T-cell malignancies: does cellular ... In this review we discuss the current state of CAR-T treatment for T-ALL and T cell lymphomas, highlighting recent novel clinical data for T cell malignancies.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19004

Long-term outcomes of CAR-T cell therapy in DLBCL. Efficacy: Complete remission occurred in 59% with a median response duration of 8.3 months. Safety profile: CRS occurred in 100% of patients, ...

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01568-z

Advances in CAR-T-cell therapy in T-cell malignancies These findings indicate that CD5 CAR-T-cell therapy can safely elicit clinical responses in patients with CD5-positive T-cell lymphomas without ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10100620/

Long-term outcomes following CAR T cell therapy These CAR T cells have also generated CR rates of 71–81% in multicentre clinical trials involving patients with R/R B cell acute lymphoblastic ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)00039-X/abstract

the long-term safety of autologous chimeric antigen ... Engineering a patient's own T cells to express chimeric antigen receptors (CARs) has cured patients with cancer refractory to all treatments.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT07055477

NCT07055477 | A Phase I Trial Anti-CC Chemokine ... 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 ...

9. nature.com nature.com/articles/s41408-024-01193-6

Impact of T cell characteristics on CAR-T cell therapy in ... In addition, rates of unsuccessful CAR-T cell manufacture are approximately 25% for non-Hodgkin's lymphoma (NHL) patients, and 6.8% for B-ALL ...