CAR T-Cell Treatment for Lymphoma

(CASEY Trial)

Not yet 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: High dose steroids

Disqualifiers: APL, Active infection, HIV, 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: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain blood cancers, such as acute myeloid leukemia, that have not responded to other treatments. The treatment uses specially designed immune cells, called CAR T-cells (C7R-EBV T cells), to target and kill cancer cells with a protein called CD70. Researchers aim to find a safe dose, identify any side effects, and determine if this approach effectively fights the cancer. Individuals with CD70-positive leukemia who have not had success with other treatments might be suitable for this trial. As a Phase 1 trial, this 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 must not have had systemic chemotherapy for at least 2 weeks before starting the study and should be recovered from any acute side effects of previous treatments.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that C7R-EBV T cells effectively control lymphoma in animal studies. These cells are a type of CAR T-cell, specially modified immune cells designed to better find and attack cancer cells.

In studies with similar T-cell treatments, patients have demonstrated that these therapies can be well-tolerated. However, since this study is in its early stages, the main goal is to find a safe dose and understand any potential side effects. So far, T-cell treatments have sometimes caused side effects like fever, low blood pressure, or difficulty breathing, but medical care can often manage these issues.

This treatment remains investigational, meaning the FDA has not yet approved it specifically for this use. However, similar treatments have been used safely in other conditions. Joining a clinical trial can help researchers learn and improve these therapies for the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma, which often include chemotherapy and radiation, the C7R-EBV T cells offer a unique approach by using genetically modified T cells to target cancer cells. These T cells are engineered to recognize and attack the cells harboring the Epstein-Barr virus, which is associated with certain types of lymphoma. Researchers are excited about this treatment because it offers a more personalized and targeted attack on the cancer cells, potentially leading to fewer side effects and improved outcomes for patients.

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

Research shows that special immune cells called C7R-EBV T cells hold promise in fighting blood cancers. In this trial, participants will receive C7R-EBV T cells, designed to find and kill cancer cells by recognizing a specific protein called CD70. Studies indicate that these T cells, equipped with a modified receptor known as C7R, can survive longer and work more effectively in the body. This enhances their ability to attack and destroy cancer cells. In lab tests, they successfully controlled lymphoma and other blood cancers in animals. ^{1 2 6 7 8}

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 patients with certain lymph gland diseases, including Hodgkin or non-Hodgkin Lymphoma, T/NK-lymphoproliferative disease, who have not responded well to existing treatments. It's particularly aimed at those whose cancer cells show signs of the Epstein Barr virus (EBV), which is linked to these conditions.

Inclusion Criteria

My cancer has returned after a period of remission.

I am 75 years old or younger.

My tumor is CD70 positive with at least 30% CD70+ cells.

Exclusion Criteria

I have been diagnosed with acute promyelocytic leukemia.

I do not have an active second cancer or was treated for another cancer within the last 2 years.

I do not have an active HIV or HTLV infection.

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 infusion, with or without lymphodepletion chemotherapy

1 day

1 visit (in-person)

Initial Follow-up

Patients are monitored for side effects and effectiveness of the T-cell infusion

6 weeks

Visits at weeks 1, 2, 4, and 6 (in-person)

Extended Follow-up

Long-term monitoring for safety and effectiveness, including annual follow-ups for 15 years

15 years

Annual visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• C7R-EBV T cells

Trial Overview The study tests a new gene therapy using modified T cells that target EBV-infected tumor cells. These T cells are engineered with a C7R gene to help them survive longer and potentially improve their ability to fight the cancer. The goal is to determine the safest high dose and its effectiveness against the cancer.

How Is the Trial Designed?

Group I: Treatment Arm A Experimental Treatment 1 Intervention

Patients will initially be consented for procurement of blood for generation of the transduced T-cells. Three dose levels will be evaluated and a possible dose level -1 in case of unexpected toxicity at dose level 1. Each patient will receive one T cell infusion.

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Antigen-specific cytotoxic T lymphocytes (CTLs) generated from induced pluripotent stem cells show rejuvenated function and strong antitumor effects against Epstein-Barr virus (EBV)-associated lymphomas, which are common in Asia and have a poor prognosis.

The study developed allogeneic EBV-specific CTLs for potential 'off-the-shelf' therapy, making it feasible for clinical use in treating these lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Induced pluripotent stem cell-derived rejuvenated cytotoxic T lymphocyte therapy for Epstein-Barr virus-associated lymphomas: application to clinical practice]. Ando, M.[2022]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10649234/

Constitutive Interleukin-7 Cytokine Signaling Enhances the ... We previously showed that a constitutively active IL7 receptor (C7R) enhanced the persistence, expansion, and anti-tumor activity of T-cells expressing ...

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. 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 ...

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

EBV‐positive diffuse large B‐cell lymphoma, not otherwise ... Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane ...

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 ...

8. 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 ...