CAR T-Cell Treatment for Lymphoma

(CASEY 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: 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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is for patients that have lymph gland disease called Hodgkin or non-Hodgkin Lymphoma or T/NK-lymphoproliferative disease and the patients condition has come back or has not gone away after treatment, including the best treatment we know for these diseases. Some patients with Lymphoma or T/NK-lymphoproliferative disease show signs of virus that is sometimes called Epstein Barr virus (EBV). This virus causes mononucleosis or glandular fever ("mono") before or at the time of their diagnosis. EBV is found in the cancer cells of up to half the patients with Hodgkin's and non-Hodgkin Lymphoma. This suggests that the EBV plays a role in causing Lymphoma. The cancer cells (in lymphoma) and some immune system cells infected by EBV are able to hide from the body's immune system and escape destruction. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. T cells have been used to treat patients with cancers. T cells, that have been trained to kill EBV infected cells can survive in blood and affect the tumor. We have treated over 80 people on studies using T cells to target these diseases. About half of those patients who had disease at the time they got the cells had responses including some patients with complete responses (meaning the cancer could no longer be detected). We think that if T cells are able to last longer in the body, they may have a better chance of killing EBV and EBV infected tumor cells. Therefore, in this study we will add a new gene to the EBV T cells that can cause the cells to live longer called C7R. We know that T cells need substances called cytokines (substances such as proteins released by specific cells of the immune system) to survive and that the cells may not get enough cytokines after the cells are infused into the body. We have added the gene C7R that gives the cells a constant supply of cytokine and helps them to survive for a longer period of time. 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 blood and what affect they have on the cancer.

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.

What data supports the effectiveness of the CAR T-Cell Treatment for Lymphoma using C7R-EBV T cells?

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 persisted longer than unmodified cells. Additionally, EBV-specific T cells have shown clinical success in treating EBV-associated cancers, suggesting potential effectiveness for this treatment. ^{1 2 3 4 5}

Is CAR T-Cell Treatment for Lymphoma safe for humans?

Research shows that EBV-specific T-cell therapies, including those modified with C7R, have been used safely in humans, with no toxic effects reported in clinical trials for EBV-related diseases. These therapies have been effective in reducing viral levels and preventing lymphoma in high-risk patients. ^{1 2 5 6 7}

How is the C7R-EBV T-cell treatment different from other treatments for lymphoma?

The C7R-EBV T-cell treatment is unique because it uses genetically modified T-cells that are enhanced with a special receptor (C7R) to improve their persistence and effectiveness against Epstein-Barr virus (EBV)-associated lymphomas, offering a targeted approach that may be more effective than traditional therapies. ^{1 2 3 5 8}

Research Team

Bilal Omer, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Immunotherapy for EBV-associated malignancies. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Constitutive Interleukin-7 Cytokine Signaling Enhances the Persistence of Epstein-Barr Virus-Specific T-Cells. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

T cell therapies. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Feasibility of cellular adoptive immunotherapy for Epstein-Barr virus-associated lymphomas using haploidentical donors. [2007]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. Japan 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]. [2022]

7. United States 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. [2022]