Tabelecleucel for EBV Associated Diseases

Recruiting at 38 trial locations

Overseen By Cindy Jachym

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Pierre Fabre Medicament

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called tabelecleucel (EBV-targeted T-cell therapy) for individuals with diseases linked to the Epstein-Barr virus (EBV), such as certain cancers and immune system issues. Researchers aim to evaluate the effectiveness and safety of tabelecleucel for these EBV-related conditions. Suitable candidates for the trial have EBV-related disorders, like certain cancers, and cannot use standard treatments such as chemotherapy. Participants must have experienced issues with their condition despite previous treatments or have conditions unsuitable for standard first-line therapy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that tabelecleucel is promising in terms of safety for people with EBV-related diseases. Other studies have found that tabelecleucel is generally safe and well-tolerated by patients. Reports highlight that patients experienced long-lasting benefits, with positive effects continuing over time. This treatment uses donor cells to help the immune system target and destroy virus-infected cells.

Although specific details about side effects weren't provided, tabelecleucel's good safety record in previous research is encouraging. This suggests that the treatment is generally considered safe for humans so far. However, as with any medical treatment, individual experiences may vary, and discussing any concerns with healthcare providers is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for EBV-associated diseases?

Unlike the standard treatments for EBV-associated diseases, which often involve rituximab or chemotherapy, tabelecleucel offers a unique approach by harnessing the power of T-cells. These are specialized cells from the immune system that are designed to target and destroy cells infected by Epstein-Barr Virus (EBV). Researchers are excited about this treatment because it could provide a more targeted attack on the virus, potentially reducing the side effects commonly associated with broader-acting therapies like chemotherapy. Additionally, tabelecleucel's use of intravenous delivery allows it to be administered directly into the bloodstream, aiming for faster and potentially more effective results.

What evidence suggests that tabelecleucel might be an effective treatment for EBV-associated diseases?

Research shows that tabelecleucel holds promise for treating diseases linked to the Epstein-Barr virus (EBV). Studies have found that it can offer lasting benefits for patients with EBV-positive post-transplant lymphoproliferative disorder (PTLD), a condition where abnormal cells grow due to a virus after an organ or stem cell transplant. In this trial, participants with various EBV-associated conditions, such as EBV+ CNS PTLD, EBV+ sarcoma, and EBV+ AID LPD, will receive tabelecleucel. As a type of immunotherapy, tabelecleucel helps the body's immune system fight the disease. It has proven safe and effective for individuals who haven't responded well to other treatments. This treatment is especially important for those unable to use standard first-line therapies. Overall, evidence suggests that tabelecleucel could be a valuable option for managing EBV-related conditions. ^{1 2 3 5 6}

Who Is on the Research Team?

Anke Friedetzky

Principal Investigator

Pierre Fabre Laboratories

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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?

Pierre Fabre Medicament

Lead Sponsor

Trials

83

Recruited

90,400+

Marie-Andrée Gamache

Pierre Fabre Medicament

Chief Executive Officer

MBA from HEC Montréal

Dr. Núria Perez-Cullell

Pierre Fabre Medicament

Chief Medical Officer since 2022

PhD in Pharmacy from the University of Barcelona

Atara Biotherapeutics

Lead Sponsor

Trials

14

Recruited

740+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04554914

NCT04554914 | A Study to Evaluate Tabelecleucel in ... Tabelecleucel is being investigated as an off-the-shelf, allogeneic T-cell immunotherapy for the treatment of EBV+ malignancies and diseases. Other Names: tab- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11215195/

Tabelecleucel for EBV+ PTLD after allogeneic HCT or SOT in ... Tabelecleucel has a favorable safety profile and shows durable clinical benefit in R/R EBV + PTLD after HCT or SOT.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03394365

Study Details | NCT03394365 | Tabelecleucel for Solid ... This is a multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT-R and ...

4. icer.org icer.org/wp-content/uploads/2024/12/ICER_EBV-PTLD_Final-Evidence-Report_For-Publication_121624.pdf

Tabelecleucel for Epstein-Barr Virus Positive Post- ... combinations of rituximab and chemotherapy or EBV-specific cytotoxic T-cell (CTL) therapy are recommended. The recommended dosing of ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204523006496

Tabelecleucel for allogeneic haematopoietic stem-cell or ... Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein–Barr virus-positive post-transplant lymphoproliferative ...

6. targetedonc.com targetedonc.com/view/tabelecleucel-advances-in-ebv-ptld-with-phase-3-trial-and-fda-resubmission

Tabelecleucel Advances in EBV+ PTLD With Phase 3 Trial ... Tab-cel is a donor-derived, EBV-specific, cytotoxic T-cell therapy designed to recognize and eliminate EBV-infected cells in immunocompromised ...