Tabelecleucel for EBV Associated Diseases

Recruiting at 33 trial locations

Overseen By Study Director

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Atara Biotherapeutics

Must not be taking: Daily steroids, Methotrexate

Disqualifiers: Active infections, HIV, GvHD, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Up to 12 months

190 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop all current medications, but it does mention a 'washout period' (time without taking certain medications) for some treatments. You may need to stop certain therapies, especially if they could affect the study drug, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Tabelecleucel for EBV-associated diseases?

Tabelecleucel has shown effectiveness in treating EBV-associated diseases, particularly in patients with post-transplant lymphoproliferative disorder (PTLD) who did not respond to other treatments. It works by targeting and eliminating cells infected with the Epstein-Barr virus, and has been used successfully in patients with other EBV-related conditions like Hodgkin's lymphoma and nasopharyngeal carcinoma. ^{1 2 3 4 5}

Is Tabelecleucel safe for humans?

Tabelecleucel, also known as Ebvallo or ATA-129, has been used safely in humans for treating certain Epstein-Barr virus (EBV)-related conditions. In studies, patients treated with EBV-specific cytotoxic T cells, similar to Tabelecleucel, did not experience significant toxicity, suggesting it is generally safe. ^{2 3 5 6 7}

What makes the treatment Tabelecleucel unique for EBV associated diseases?

Tabelecleucel is unique because it is an allogeneic (from a donor) T-cell therapy specifically designed to target and eliminate cells infected with the Epstein-Barr virus (EBV) in a precise manner. Unlike other treatments, it uses EBV-specific T-cells to restore the immune system's ability to fight EBV-related diseases, especially in patients who have not responded to other therapies. ^{1 2 3 6 8}

What is the purpose of this trial?

This trial tests tabelecleucel, a treatment using special immune cells, in patients with certain diseases related to the Epstein-Barr virus (EBV) who can't use or don't respond to standard treatments. It works by enhancing the immune system's ability to attack virus-infected cells. Tabelecleucel is being tested for recurring or hard-to-treat EBV-related diseases.

Research Team

Justin Wahlstrom, MD

Principal Investigator

Atara Biotherapeutics

Eligibility Criteria

This trial is for individuals with Epstein-Barr virus-associated diseases, including those who have had stem cell or organ transplants and are experiencing complications. Participants should have measurable disease, be planning definitive therapy, and have a performance status indicating they can perform daily activities. They must not be pregnant, breastfeeding, or require high doses of steroids.

Inclusion Criteria

My cancer can be measured by tests in my body or brain.

I am scheduled for a definitive treatment like a stem cell transplant or gene therapy for my primary immunodeficiency.

My organs work well, unless the issue is caused by my EBV-related disease.

Exclusion Criteria

I require medication to maintain my blood pressure or need help to breathe.

I have a severe reaction from a transplant, known as GvHD.

I haven't had certain cell therapies or treatments that affect immune cells within the last 8 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tabelecleucel intravenously weekly for 3 weeks in 35-day cycles until maximal response, disease progression, or unacceptable toxicity

Up to 12 months

Weekly visits for 3 weeks per cycle

Safety Follow-up

Participants complete a safety follow-up visit 30 days after the last dose

1 month

1 visit (in-person)

Quarterly Follow-up

Participants are assessed every 3 months for disease response until the end of study visit at 24 months after the first dose

24 months

Quarterly visits

Treatment Details

Interventions

• Tabelecleucel

Trial Overview The study is testing the effectiveness and safety of tabelecleucel in treating various EBV-associated conditions. Tabelecleucel is an investigational treatment aimed at targeting cells infected with the Epstein-Barr virus to help manage these diseases.

Participant Groups

Group I: EBV+ sarcoma, including LMS, or smooth muscle tumors Experimental Treatment 1 Intervention

Participants with newly diagnosed EBV+ sarcoma for whom the standard first-line therapy is inappropriate, including LMS or smooth muscle tumor, will receive IV tabelecleucel.

Group II: EBV+ PTLD (inappropriate for first-line therapy or CD20-negative) Experimental Treatment 1 Intervention

Participants with EBV+ PTLD for whom standard first-line therapy (rituximab or chemotherapy) is inappropriate, including CD20-negative disease, will receive IV tabelecleucel.

Group III: EBV+ PID LPD Experimental Treatment 1 Intervention

Participants with R/R or newly diagnosed EBV+ PID LPD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.

Group IV: EBV+ CNS PTLD Experimental Treatment 1 Intervention

Participants with R/R or newly diagnosed EBV+ CNS PTLD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.

Group V: EBV+ AID LPD Experimental Treatment 1 Intervention

Participants with R/R or newly diagnosed EBV+ AID LPD for whom standard first-line therapy is inappropriate, will receive IV tabelecleucel.

Tabelecleucel is already approved in European Union, United Kingdom, Switzerland for the following indications:

Approved in European Union as Ebvallo for:

• Relapsed or refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD)

Approved in United Kingdom as Ebvallo for:

• Relapsed or refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD)

Approved in Switzerland as Ebvallo for:

• Relapsed or refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD)

Who Is Running the Clinical Trial?

Atara Biotherapeutics

Lead Sponsor

Trials

14

Recruited

740+

Findings from Research

Adoptive immune transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTL) shows promise as a treatment for EBV-associated lymphoproliferative disorders, particularly in patients who have undergone bone marrow transplantation.

This immunotherapy approach has also been applied successfully in a patient with severe chronic active EBV infection, highlighting its potential for broader clinical use in managing EBV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adoptive immune therapy using EBV-specific CTL]. Kuzushima, K., Morishima, T.[2011]

Tabelecleucel (EbvalloTM) is an innovative T-cell immunotherapy specifically designed to target and eliminate Epstein-Barr virus (EBV)-positive cells, approved for treating relapsed or refractory EBV+ post-transplant lymphoproliferative disease (PTLD) in patients aged 2 and older.

It received marketing authorization under 'exceptional circumstances' on December 16, 2022, highlighting its potential as a treatment option for patients who have not responded to at least one prior therapy, including chemotherapy for solid organ transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tabelecleucel: First Approval. Keam, SJ.[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]

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]

Cytotoxic T cell (CTL)-based immunotherapy is a promising alternative to traditional radiotherapy and chemotherapy for treating tumors, as it specifically targets antigens found in malignant cells, potentially reducing side effects.

Recent successes in using CTL-based therapy for Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) highlight its potential for treating other EBV-related cancers, where the antigens are well-defined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of cytotoxic T lymphocytes for immunotherapy of EBV-associated malignancies. Smith, C., Khanna, R.[2020]

Adoptive immunotherapy using ex vivo-expanded EBV-specific cytotoxic T lymphocytes (EBV-CTLs) was successfully generated from all 8 patients with mild/moderate chronic active Epstein-Barr virus (CAEBV) infection, leading to significant clinical improvements such as resolution of fatigue, fever, and lymphadenopathy.

The treatment was well-tolerated with no observed toxicity, and 4 out of 5 treated patients did not experience disease relapse for 6 to 36 months, suggesting that EBV-CTL therapy could be a safe and effective option for managing mild/moderate CAEBV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection. Savoldo, B., Huls, MH., Liu, Z., et al.[2022]

In a study of seven patients with Chronic Active Epstein-Barr Virus Infection (CAEBV), four showed the presence of EBV-specific cytotoxic T lymphocytes (CTLs) in their blood, indicating a potential immune response, while three did not have detectable CTLs.

The presence of EBV-specific CTLs was more common in patients with active disease, and in two patients who initially lacked these CTLs, they reappeared after treatment with allogeneic bone marrow transplantation, suggesting that CTL failure may contribute to the development of CAEBV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virus-specific cytotoxic T cells in chronic active Epstein-Barr virus infection. Shibayama, H., Imadome, KI., Onozawa, E., et al.[2017]

Dendritic cells (DCs) loaded with disrupted EBV-transformed B-lymphoblastoid cell lines (BLCLs) significantly enhanced the generation of EBV-specific cytotoxic T lymphocytes (CTLs), achieving a lytic activity of 78%, which was statistically significant compared to other methods.

This improved lytic activity suggests that using DCs for generating EBV-specific CTLs could be a promising immunotherapy for patients at risk of EBV-associated lymphoma after solid organ transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells improve the generation of Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of posttransplantation lymphoma. Wheatley, GH., McKinnon, KP., Iacobucci, M., et al.[2015]

References

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

[Adoptive immune therapy using EBV-specific CTL]. [2011]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Tabelecleucel: First Approval. [2023]

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

T cell therapies. [2019]

4. Japan pubmed.ncbi.nlm.nih.gov

Immunotherapy for EBV-associated malignancies. [2021]

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

Generation of cytotoxic T lymphocytes for immunotherapy of EBV-associated malignancies. [2020]

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

Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

Virus-specific cytotoxic T cells in chronic active Epstein-Barr virus infection. [2017]

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

Dendritic cells improve the generation of Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of posttransplantation lymphoma. [2015]