EBV-Specific T-Cell Therapy for Lymphoma

(CILESTE Trial)

Recruiting at 1 trial location

Overseen By Bilal Omer, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Systemic corticosteroids

Disqualifiers: Pregnancy, Infections, Airway obstruction, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals with certain types of lymphoma that persist or recur after standard treatments. The focus is on lymphoma cases associated with the Epstein-Barr virus (EBV), which can hide in the body and cause immune cells to malfunction. The trial employs special T cells, a type of white blood cell, enhanced to live longer in the body to better target and destroy EBV-infected cancer cells. Suitable candidates for this trial include patients with EBV-positive lymphoma who have ongoing or recurring disease despite previous treatments. As a Phase 1 trial, the research aims to understand 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 requires that you stop taking other investigational therapies at least 4 weeks before joining. If you are using systemic corticosteroids (like prednisone) at a dose higher than 0.5 mg/kg/day, you will need to stop those as well.

Is there any evidence suggesting that C7R-EBV T cells are likely to be safe for humans?

Research has shown that C7R-EBV T cells, specially modified to combat tumors caused by the EBV virus, have yielded positive results in studies. About half of the patients receiving these cells showed improvement, with some even achieving full recovery. These modified cells are designed to remain in the body longer, potentially enhancing their ability to fight the virus and cancer cells.

Early findings from trials indicate that these treatments are generally safe for patients. The studies aim to determine the safest dose, so researchers closely monitor any side effects or issues. As this study is in an early phase, assessing safety is standard for new treatments. However, these early results are promising, showing that most patients tolerate the treatment well. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about C7R-EBV T cells for treating lymphoma because they offer a unique approach compared to standard treatments like chemotherapy and radiation. Unlike traditional therapies that target cancer cells broadly, C7R-EBV T cells are engineered to specifically attack cells infected with the Epstein-Barr virus (EBV), which is associated with certain types of lymphoma. This targeted action could potentially lead to fewer side effects and improve treatment effectiveness. Additionally, one arm of the trial tests these T cells without prior lymphodepletion chemotherapy, which might offer a gentler option for patients.

What evidence suggests that C7R-EBV T cells might be an effective treatment for lymphoma?

Research has shown that C7R-EBV T cells, specially modified for enhanced performance, effectively control lymphoma in animal studies. In earlier research, about half of the patients who received these enhanced T cells showed positive results, with some even experiencing complete remission. The C7R gene helps these T cells live longer in the body by providing a steady nutrient supply, boosting their ability to fight the virus and cancer cells linked to the Epstein Barr virus (EBV). This method targets and destroys EBV-infected cells, often found in certain types of lymphoma.

In this trial, participants will receive C7R-EBV T cells either with or without lymphodepletion chemotherapy. Overall, these findings suggest that C7R-EBV T cells could be promising for treating EBV-related lymphomas. ^{1 2 4 6 7}

Who Is on the Research Team?

Bilal Omer, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with EBV-positive Hodgkin's or non-Hodgkin's Lymphoma, or T/NK-lymphoproliferative disease that persists after treatment. Participants must have certain blood and organ function levels, weigh at least 10 kg, have a life expectancy of over 6 weeks, and not be on systemic steroids or pregnant.

Inclusion Criteria

Patients with life expectancy ≥ 6 weeks

My blood tests for liver and kidney function, and hemoglobin levels are within the required limits.

Patients should have been off other investigational therapy for 4 weeks prior to entry in this study.

Exclusion Criteria

My condition is causing or could soon block my airways due to its size.

Known pregnancy or actively breastfeeding (pregnancy test is not required at the time of procurement).

You are currently pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive C7R EBV T cells, possibly with cyclophosphamide and fludarabine chemotherapy

2 weeks

Multiple visits (in-person) for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with scheduled visits and disease evaluations

15 years

Scheduled visits at weeks 2, 4, 6; months 3, 6, 9, 12; annually thereafter

Optional Additional Dose

Eligible participants may receive an additional dose of C7R EBV T cells if disease has not worsened

6 weeks between doses

1 visit (in-person) for infusion

What Are the Treatments Tested in This Trial?

Interventions

• C7R-EBV T cells

Trial Overview The study tests different doses of genetically modified T cells (C7R-EBV T cells) designed to last longer in the body and fight EBV-infected tumor cells. The goal is to determine the highest safe dose, how long these cells can be detected in the blood, and their effect on cancer.

How Is the Trial Designed?

Group I: Arm B: Treatment with lymphodepletion chemotherapy Experimental Treatment 2 Interventions

C7R-EBVSTs with lymphodepletion chemotherapy

Group II: Arm A: Treatment without lymphodepletion chemotherapy Experimental Treatment 3 Interventions

C7R-EBVSTs Group B will be activated if only limited expansion and clinical efficacy is observed in Group A

C7R-EBV T cells is already approved in United States, European Union for the following indications:

Approved in United States as EBV-specific T cells for:

• Hodgkin lymphoma
• Non-Hodgkin lymphoma
• T/NK-lymphoproliferative disease

Approved in European Union as EBV-specific T cells for:

• Post-transplant lymphoproliferative disease (PTLD)
• Hodgkin lymphoma
• Non-Hodgkin lymphoma

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Texas Children's Hospital

Collaborator

Trials

2

Recruited

10,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Polyclonal Epstein-Barr virus (EBV)-specific cytotoxic T cells (CTL) have shown promise in treating EBV-associated malignancies, indicating their potential effectiveness in targeting specific cancers.

The chapter discusses strategies to enhance the antitumor activity of these EBV-specific CTLs, which could lead to improved T cell therapies for various tumors with known antigens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell therapies. Gottschalk, S., Bollard, CM., Straathof, KC., et al.[2019]

Two cord blood transplant recipients with life-threatening EBV(+) lymphomas achieved complete remission after receiving infusions of third-party EBV-specific cytotoxic T lymphocytes (CTLs), demonstrating the efficacy of this treatment approach.

Both patients remained free of toxicity and graft-versus-host disease, surviving without recurrence for 20 and 15 months post-treatment, suggesting that this method could be a viable option for treating similar conditions in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Barker, JN., Doubrovina, E., Sauter, C., et al.[2022]

Transgenic T cells expressing specific T cell receptors (TCRs) targeting Epstein-Barr virus (EBV) antigens show promise in treating EBV-associated lymphomas and carcinomas, potentially offering a more selective approach than traditional therapies.

This method may reduce collateral damage to healthy cells compared to chimeric antigen receptor (CAR) therapies that target general B cell markers, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redirecting T Cells against Epstein-Barr Virus Infection and Associated Oncogenesis. Münz, C.[2021]

A new strategy for creating EBV-specific cytotoxic T cell therapy lines shows strong effectiveness in targeting EBV-associated lymphomas, particularly after bone marrow or solid organ transplants.

This method involves stimulating peripheral blood mononuclear cells with irradiated EBV-transformed cells, resulting in T cell lines that specifically kill EBV-positive targets while sparing non-EBV targets, highlighting a targeted approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of cellular adoptive immunotherapy for Epstein-Barr virus-associated lymphomas using haploidentical donors. Orentas, RJ., Lemas, MV., Mullin, MJ., et al.[2007]

The Epstein-Barr virus (EBV) can evade the immune system and cause various cancers, but its viral antigens make these cancers suitable targets for immunotherapy.

Infusing EBV-specific cytotoxic T lymphocytes has been shown to be safe and effective, helping to restore anti-virus immunity in patients with EBV-related malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The interplay between Epstein-Barr virus and the immune system: a rationale for adoptive cell therapy of EBV-related disorders. Merlo, A., Turrini, R., Dolcetti, R., et al.[2022]

The study demonstrated that modifying Epstein-Barr virus-specific T-cells (EBVSTs) with a constitutively active IL7 receptor (C7R) significantly enhances their expansion and anti-tumor activity, showing promise for treating EBV-associated malignancies.

C7R-EBVSTs exhibited improved lymphoma control in a mouse model compared to unmodified T-cells, leading to the initiation of a clinical trial for patients with refractory or relapsed EBV-positive lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Constitutive Interleukin-7 Cytokine Signaling Enhances the Persistence of Epstein-Barr Virus-Specific T-Cells. Sharma, S., Sauer, T., Omer, BA., et al.[2023]

Over 250 patients with EBV-related diseases have safely received virus-specific cytotoxic T lymphocyte (CTL) therapy, showing effectiveness and achieving complete remissions even in those who did not respond to standard treatments.

The success of EBV-specific CTL therapy has led to its application in various EBV-related conditions, such as Hodgkin's lymphoma and nasopharyngeal carcinoma, and advancements in CTL generation techniques are expanding its potential to target other viral infections and non-EBV related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for EBV-associated malignancies. Merlo, A., Turrini, R., Dolcetti, R., et al.[2021]

In a study involving 39 high-risk patients receiving donor-derived EBV-specific T cells, the treatment was found to be safe and effective in preventing EBV-related immunoblastic lymphoma, with no toxic effects reported from the T-cell therapy.

Patients with high levels of EBV-DNA showed significant decreases in viral levels after receiving the T-cell infusions, and none of these patients developed lymphoma, demonstrating the antiviral efficacy of the donor-derived T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Rooney, CM., Smith, CA., Ng, CY., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11649625/

Role of rapidly evolving immunotherapy in chronic active ... found that the constitutive Interleukin-7 receptor (C7R) can enhance the persistence, amplification, and anti-tumor activity of EBV-specific T ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-08324

Genetically-Modified Immune Cells (C7R-expressing ... If T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected cancer cells. T-cell therapy is a type of ...

3. withpower.com withpower.com/trial/phase-1-leukemia-3-2024-2d79b

CAR T-Cell Treatment for Lymphoma (CASEY Trial) Research shows that C7R-EBV T cells, which are modified to enhance their activity, have been effective in controlling lymphoma in animal models and have ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/ajh.27430

EBV‐positive diffuse large B‐cell lymphoma, not otherwise ... Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04664179?term=Texas%20Children's%20Hospital&cond=%22Immunoproliferative%20Disorders%22&aggFilters=status:&viewType=Table&rank=9

EBV Specific T-Lymphocytes for Treatment of EBV-Positive ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1988944/

Epstein Barr virus–specific cytotoxic T lymphocytes expressing ... Adoptive transfer of Epstein Barr virus (EBV)–specific cytotoxic T-lymphocytes (EBV-CTLs) has shown that these cells persist in patients with EBV + Hodgkin ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/262582

EBV Specific T-Lymphocytes for Treatment of EBV-Positive ... The purpose of this study is to find the largest safe dose of C7R-EBV T cells, and additionally to evaluate how long they can be detected in the ...