Tabelecleucel for Post-Transplant Cancer

(ALLELE Trial)

Recruiting in Palo Alto (17 mi)

+64 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Atara Biotherapeutics

Must not be taking: Daily steroids, Methotrexate

Disqualifiers: Burkitt lymphoma, Hodgkin lymphoma, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.

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.

What data supports the effectiveness of the treatment Tabelecleucel for post-transplant cancer?

Tabelecleucel has shown effectiveness in treating post-transplant lymphoproliferative disorders (PTLD) by targeting and eliminating cells infected with the Epstein-Barr virus (EBV). In studies, it has helped some patients achieve complete remission, even when other treatments failed, and it works by using specially prepared immune cells to fight the virus-infected cells. ^{1 2 3 4 5}

Is Tabelecleucel (Ebvallo) safe for human use?

Tabelecleucel, also known as Ebvallo, has been used in clinical trials for treating certain EBV-related diseases and has been generally well tolerated. In studies, patients experienced some side effects like fever and rash, but serious complications like graft-vs-host disease were not observed, indicating a good safety profile. ^{1 2 6 7 8}

What makes the treatment Tabelecleucel unique for post-transplant cancer?

Tabelecleucel is unique because it is an allogeneic (donor-derived) Epstein-Barr virus-specific T-cell therapy that targets and eliminates EBV-positive cells, offering a novel approach for patients with relapsed or refractory post-transplant lymphoproliferative disease (PTLD) who have not responded to other treatments. Unlike traditional therapies, it provides immediate accessibility and has shown effectiveness even in patients who have undergone multiple prior therapies. ^{1 2 3 5 9}

Research Team

Aditi Mehta, DO

Principal Investigator

Atara Biotherapeutics

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Tabelecleucel (CAR T-cell Therapy)

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.

Participant Groups

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 Switzerland for the following indications:

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

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 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]

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 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]

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]

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]

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]

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]

References

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

Tabelecleucel: First Approval. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

T cell therapies. [2019]

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

Immunity, homing and efficacy of allogeneic adoptive immunotherapy for posttransplant lymphoproliferative disorders. [2023]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Treatment options for post-transplant lymphoproliferative disorder and other Epstein-Barr virus-associated malignancies. [2019]

6. Germany 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. [2022]

7. England 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. [2020]

8. Japan pubmed.ncbi.nlm.nih.gov

Immunotherapy for EBV-associated malignancies. [2021]

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

Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells. [2019]