Tabelecleucel for Post-Transplant Cancer

(ALLELE Trial)

Recruiting at 68 trial locations

Overseen By Claire Fabre

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Pierre Fabre Medicament

Must not be taking: Daily steroids, Methotrexate

Disqualifiers: Burkitt lymphoma, Hodgkin lymphoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 3

Duration: 5 weeks per cycle

115 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines tabelecleucel, a new treatment for EBV+ PTLD, a type of cancer that can occur after organ or stem cell transplants. The goal is to determine if tabelecleucel is safe and effective for those whose previous treatments, such as rituximab or chemotherapy, were unsuccessful. The trial includes different groups: one for individuals with solid organ transplants and another for those with stem cell transplants. Suitable candidates have undergone these types of transplants, have been diagnosed with EBV+ PTLD, and have not responded to other treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on daily steroids over a certain dose, ongoing methotrexate, or certain other treatments. 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?

Studies have shown that tabelecleucel is generally well-tolerated. In earlier research, patients received tabelecleucel for Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (EBV+ PTLD). Most patients did not experience severe side effects. Common mild side effects included tiredness and fever, while serious side effects were rare.

Further studies suggest that tabelecleucel could be a promising option for those who have not responded to rituximab treatments. Although this treatment is still under investigation, its ongoing evaluation in advanced trials indicates reasonable safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tabelecleucel is unique because it targets Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (EBV+ PTLD) using a novel mechanism. Unlike standard treatments such as rituximab or chemotherapy, which attack cancer cells more broadly, tabelecleucel uses EBV-specific T cells to home in on and destroy EBV-infected cells specifically. This targeted approach not only promises higher effectiveness but also may reduce unwanted side effects common with conventional therapies. Researchers are excited about tabelecleucel because it offers hope for patients whose PTLD has not responded to existing treatments.

What evidence suggests that tabelecleucel might be an effective treatment for post-transplant cancer?

Research shows that tabelecleucel may help treat Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD). This treatment uses special cells to locate and destroy virus-infected cells, aiding the body's defense. Participants in this trial will receive tabelecleucel if they have EBV+ PTLD following a solid organ transplant (SOT) or hematopoietic cell transplant (HCT) that has not responded to previous treatments like rituximab or chemotherapy. Earlier studies have shown positive results for patients who used tabelecleucel after other treatments failed, with reports indicating significant disease reduction in these challenging cases. Overall, evidence suggests it could be beneficial when other treatments have not succeeded. ^{1 2 3 6 7}

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 people who've had a solid organ or stem cell transplant and now have a condition called EBV+ PTLD, which hasn't improved after treatment with Rituximab alone or with chemotherapy. Participants must be in stable condition without the need for intensive support like ventilators, not have certain other diseases or ongoing severe infections, and women of childbearing age must agree to use effective contraception.

Inclusion Criteria

I have been diagnosed with EBV+ PTLD through a biopsy.

My organs are working well.

My cancer shows up on scans and is actively growing.

Exclusion Criteria

I have not received T cell antibody therapy in the last 4 weeks.

My condition is either Burkitt lymphoma, classical Hodgkin lymphoma, or a T cell lymphoma.

I am not on high doses of steroids, methotrexate, or undergoing photopheresis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous tabelecleucel at a dose of 2 × 10^6 cells/kg on Days 1, 8, and 15 of each 5-week cycle

5 weeks per cycle

3 visits per cycle (in-person)

Follow-up

Participants are monitored for disease and survival status

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Tabelecleucel

Trial Overview The study is testing tabelecleucel's effectiveness and safety in treating EBV+ PTLD among those who've undergone either solid organ transplants (like kidney, liver) or allogeneic hematopoietic cell transplants (stem cells from donors). The participants should have previously tried treatments that didn't work well enough.

How Is the Trial Designed?

Group I: Cohort SOT-R+C (C-SOT-R+C) Experimental Treatment 1 Intervention

Participants with EBV+ PTLD following SOT that has failed both rituximab and chemotherapy will receive IV tabelecleucel.

Group II: Cohort SOT-R (C-SOT-R) Experimental Treatment 1 Intervention

Participants with EBV+ PTLD following SOT that has failed rituximab will receive IV tabelecleucel.

Group III: Cohort HCT (C-HCT) Experimental Treatment 1 Intervention

Participants with EBV+ PTLD following HCT that has failed rituximab containing regimen 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

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]

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]

An 18-month-old patient with EBV-positive posttransplant lymphoproliferative disease (PTLD) achieved complete tumor regression after a single infusion of EBV-specific cytotoxic T lymphocytes (CTL) from an unrelated donor, with no observed toxicity or graft-versus-host disease.

The patient's EBV load became undetectable within a week, and the patient has remained in complete remission for 24 months, suggesting that this approach could be a promising antiviral and antitumor therapy for immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells. Haque, T., Taylor, C., Wilkie, GM., 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 9 patients with refractory or recurrent angioimmunoblastic T-cell lymphoma (AITL), EBV-specific CTL therapy demonstrated a 66.7% response rate, with 55.6% achieving objective remission after treatment.

The therapy was found to be safe, with only mild side effects like fever and rash reported, and no cases of graft-versus-host disease, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of Epstein-Barr virus-specific antigen peptide-activated cytotoxic T-cells treatment for refractory or recurrent angioimmunoblastic T-cell lymphoma: A prospective clinical observational study. Bingjie, W., Lihong, W., Yongjin, S., et al.[2020]

Adoptive immunotherapy using allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (allo-CTL) showed promising results in treating aggressive, advanced monoclonal posttransplant lymphoproliferative disorders (PTLD) in three patients who were resistant to multiple therapies, with two achieving complete remission.

The treatment was well-tolerated with minimal toxicity, and there was evidence of antiviral efficacy and reconstitution of EBV-specific immunity, suggesting that allo-CTL could be a viable alternative to autologous CTL, especially in patients who cannot generate their own due to prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunity, homing and efficacy of allogeneic adoptive immunotherapy for posttransplant lymphoproliferative disorders. Gandhi, MK., Wilkie, GM., Dua, U., et al.[2023]

In a phase II clinical trial involving 47 patients with advanced, relapsed ENKTL, 15 patients received the autologous EBV-specific T cell treatment (baltaleucel T), showing a 30% complete response rate and a 50% overall response rate among those with measurable disease.

Baltaleucel T was well tolerated, and responders had significantly better progression-free survival and overall survival compared to non-responders, indicating its potential efficacy as a treatment for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study. Kim, WS., Oki, Y., Kim, SJ., 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]

Adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) targeting Epstein-Barr virus (EBV) is effective in preventing and treating post-transplant lymphoproliferative disease (PTLD) in solid organ transplant recipients, providing long-term immunity against recurrence.

The review discusses the potential of EBV-specific CTLs not only for PTLD but also for other EBV-related cancers, such as Hodgkin's disease and Burkitt's lymphoma, while highlighting the challenges in customizing therapies based on individual disease characteristics and EBV antigen expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for post-transplant lymphoproliferative disorder and other Epstein-Barr virus-associated malignancies. Davis, JE., Moss, DJ.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12182446/

Tabelecleucel in Post-transplant Epstein–Barr Virus ... They recount their shared experience with tabelecleucel, a novel therapy for Epstein–Barr virus-associated post–transplant lymphoproliferative disease (EBV + ...

2. 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 ...

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. 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 ...

5. astctjournal.org astctjournal.org/article/S2666-6367(25)01383-1/fulltext

Long-Term Efficacy of Epstein-Barr Virus-Specific T Cells ... Adoptive transfer of EBV-specific cytotoxic T lymphocytes (EBV-CTLs) offers a promising strategy to restore antiviral immunity, but long-term ...

6. icer.org icer.org/wp-content/uploads/2024/09/ICER_EBV-PTLD_Draft-Report_For-Publication_091224.pdf

Tabelecleucel for Epstein-Barr Virus Positive Post- ... Effectiveness and safety outcomes in patients with. EBV+ PTLD treated with allogeneic EBV-specific T-cell immunotherapy (tabelecleucel) under.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12189535/

Adoptive Cell Immunotherapy in Relapse/Refractory Epstein ... We highlight the most robust clinical outcomes reported with EBV-CTLs, particularly those achieved with tabelecleucel, and explore emerging ...