T Cell Therapy for Lymphoma

Recruiting at 1 trial location

Overseen By Jean-Sébastien Delisle, MD, PhD

Age: Any Age

Sex: Female

Trial Phase: Academic

Sponsor: Ciusss de L'Est de l'Île de Montréal

Must not be taking: T-cell depleting antibodies

Disqualifiers: Pregnancy, Uncontrolled GVHD, 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: Unknown

Duration: 5 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special treatment using donor T cells to combat lymphoma, a type of blood cancer. The goal is to determine if these donor-derived EBV-specific T cells can aid young adults who have already undergone a stem cell transplant for lymphoma linked to the Epstein-Barr virus (EBV). Candidates who have had a stem cell transplant and are dealing with EBV-related lymphoma might be suitable, especially if they haven’t received certain antibody treatments in the last 28 days and do not have uncontrolled graft-versus-host disease (GVHD). As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for lymphoma patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have received T-cell depleting antibodies within 28 days before the trial.

What prior data suggests that Donor-Derived EBV-Specific T Cells are safe?

Research has shown that donor-derived EBV-specific T cells are generally safe for treating EBV-positive lymphomas. Studies have found that these T cells can be administered to patients who have undergone stem cell transplants, often resulting in long-lasting remission, meaning the cancer remains absent. Previous trials reported that most patients tolerate these treatments well, without major issues. Some mild side effects have been noted, but serious problems are rare. This suggests that donor-derived EBV-specific T cells are relatively safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for lymphoma, which typically includes chemotherapy, radiation, and monoclonal antibodies, the donor-derived EBV-specific T cells offer a unique approach. These T cells are engineered to specifically target and attack cells infected with the Epstein-Barr virus (EBV), which is associated with certain types of lymphoma. This targeted action means the treatment could potentially be more effective with fewer side effects compared to traditional therapies that affect both cancerous and healthy cells. Researchers are excited because this form of immunotherapy harnesses the body's own immune system, potentially offering a more precise and less toxic alternative to conventional treatments.

What evidence suggests that Donor-Derived EBV-Specific T Cells might be an effective treatment for lymphoma?

Research has shown that special immune cells from donors, called EBV-specific T cells, can help treat certain cancers linked to the Epstein-Barr virus (EBV). In some studies, these cells have made the cancer disappear and remain absent for a long time. One study found that 68% of patients were still alive one year after treatment, and this survival rate remained steady for up to five years. These T cells attack the Epstein-Barr virus, which is connected to some lymphomas. They are considered safe and can prevent and treat lymphoma after a stem cell transplant. Overall, this treatment appears promising for patients with EBV-related lymphomas. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for a young adult with systemic EBV-positive lymphoma of childhood, who has undergone allogeneic stem cell transplantation. Specific eligibility criteria are not provided.

Inclusion Criteria

Negative serum pregnancy test and use of effective contraception method.

I understand and can agree to the study's procedures and risks.

Exclusion Criteria

I haven't received T-cell depleting antibodies in the last 28 days.

Any abnormal condition or laboratory result that is considered by the Principal Investigator capable of altering patient or study outcome

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patient receives SMILE-based chemotherapy followed by myeloablative HLA-matched unrelated allogeneic stem cell transplantation and donor-derived EBV-specific T-cell infusion

5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of GVHD and disease recurrence

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Donor-Derived EBV-Specific T Cells

Trial Overview

The trial is testing donor-derived EBV-specific T cells as an immunological consolidation treatment after the patient has received a stem cell transplant.

Donor-Derived EBV-Specific T Cells is already approved in United States, European Union for the following indications:

Approved in United States as EBV-Specific T Cells for:

• Post-transplant lymphoproliferative disease (PTLD)
• EBV-related complications after hematopoietic stem cell transplantation (HSCT)

Approved in European Union as EBV-Specific T Cells for:

• EBV-positive lymphoma
• Post-transplant lymphoproliferative disease (PTLD)
• EBV-related complications after hematopoietic stem cell transplantation (HSCT)

Who Is Running the Clinical Trial?

Ciusss de L'Est de l'Île de Montréal

Lead Sponsor

Trials

81

Recruited

6,400+

Published Research Related to This Trial

Adoptive immunotherapy using virus-specific T cells from transplant donors has shown a promising disease response rate of 50-76% in treating drug-refractory EBV+ lymphomas and infections like CMV and adenovirus, with low toxicity and graft-versus-host disease (GVHD) incidences.

The review highlights the importance of the characteristics of both the viral pathogens and the T cells used, as well as the host's condition, in determining the success of the treatment, suggesting that in vitro culture can enhance the effectiveness of T cells by expanding those that target common viral epitopes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virus-specific T-cell banks for 'off the shelf' adoptive therapy of refractory infections. O'Reilly, RJ., Prockop, S., Hasan, AN., et al.[2018]

A rapid protocol for isolating EBV-specific T cells from donor blood was developed, allowing for urgent treatment of posttransplantation lymphoproliferative disease (PTLD) in patients after hematopoietic stem cell transplantation.

In a study involving 6 patients with PTLD, those who received T cells at an earlier disease stage achieved complete and stable remission, with two patients remaining free from EBV-related disease for over 2 years, highlighting the efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Moosmann, A., Bigalke, I., Tischer, J., et al.[2021]

A patient with relapsed EBV-positive Hodgkin's Disease achieved disease stabilization for 6 months after receiving gene-marked autologous EBV-specific cytotoxic T lymphocytes (CTLs), demonstrating the potential efficacy of this immunotherapy approach.

The donor-derived CTL infusion led to a complete remission 5 years post-transplant, highlighting the importance of targeting multiple EBV antigens (LMP1 and LMP2) for a stronger immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo expansion of LMP 1- and 2-specific T-cells in a patient who received donor-derived EBV-specific T-cells after allogeneic stem cell transplantation. Bollard, CM., Gottschalk, S., Huls, MH., et al.[2019]

In a study of 26 patients who underwent allogeneic hematopoietic stem-cell transplantation for EBV-associated lymphomas, donor-derived LMP-specific T cells (LMP-Ts) demonstrated a high safety profile with no immediate infusion-related toxicities and only one dose-limiting toxicity observed.

The 2-year overall survival rate was 68% overall, with 78% for patients in complete remission and 80% for those with B-cell disease, indicating that LMP-Ts are an effective adjuvant therapy that may significantly improve outcomes compared to historical survival rates of 30% to 50%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation. McLaughlin, LP., Rouce, R., Gottschalk, S., et al.[2022]

A bank of 32 virus-specific T cell lines was successfully used to treat 50 patients with severe viral infections after stem cell transplants, resulting in a 74% overall response rate within 6 weeks, demonstrating the efficacy of this approach.

The treatment was safe, with no immediate infusion-related adverse events and only 2 cases of de novo graft-versus-host disease, indicating that using banked T cell lines can be a viable option for rapid antiviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Leen, AM., Bollard, CM., Mendizabal, AM., et al.[2022]

A personalized T cell manufacturing program successfully created EBV-specific cytotoxic T lymphocyte (EBV-CTL) products for 37 patients with refractory EBV infections or malignancies, showing that this approach is feasible and can be done quickly, within a median of 5 days after donor identification.

The treatment led to a complete response in 20 out of 29 evaluated patients, with no reported infusion-related toxicity, indicating that EBV-CTL transfer is both effective and safe for immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors. Bonifacius, A., Lamottke, B., Tischer-Zimmermann, S., et al.[2023]

Infusions of donor-derived, EBV-specific cytotoxic T cells may help prevent and treat EBV-related lymphoproliferative disease in children with weakened immune systems, particularly those receiving T cell-depleted bone marrow transplants.

This approach targets the Epstein-Barr virus, which can cause serious B cell lymphomas, highlighting the potential of immunotherapy in managing viral-related cancers in vulnerable pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for Epstein-Barr virus-related lymphoma. Smith, CA., Ng, CY., Loftin, SK., et al.[2019]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10808771/

Virus-specific T-cells from third party or transplant donors for ...

More recently, EBV-specific T-cells generated from allogeneic 3rd party donors have also been shown to induce durable remission of EBV+ lymphomas in Rituximab ...

2.

astctjournal.org

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

Long-Term Efficacy of Epstein-Barr Virus-Specific T Cells ...

Donor-derived EBV-CTLs are a safe and effective treatment for EBV-PTLD following haploidentical HSCT. Our findings support the long-term ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2666636725013831

Long-Term Efficacy of Epstein-Barr Virus-Specific T Cells ...

The 1-year overall survival rate was 68.0% (95% CI, 51.3% to 80.0%), and survival remained stable without significant decline up to 5 years.

4.

nature.com

nature.com/articles/s41467-024-54595-2

Compassionate access to virus-specific T cells for adoptive ...

These results show that the compassionate use of virus-specific T cell therapy can provide therapeutic benefit, especially for patients with ...

5.

ashpublications.org

ashpublications.org/blood/article/92/5/1549/247386/Infusion-of-Cytotoxic-T-Cells-for-the-Prevention

Infusion of Cytotoxic T Cells for the Prevention and Treatment ...

Polyclonal donor-derived T-cell lines specific for EBV proteins can thus be used safely to prevent EBV-related immunoblastic lymphoma after allogeneic marrow ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38274824/

Virus-specific T-cells from third party or transplant donors for ...

Phase I and II trials have shown that in HCT recipients, adoptive transfer of EBV-specific T-cells from the HCT donor can safely induce durable remissions of ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02580539

A Study of the Safety and Efficacy of EBV Specific T-cell Lines

This study evaluates the safety and efficacy of EBV-specific T-cell lines to treat patients suffering from high EBV viral titers not responding to standard of ...