T Cell Therapy for Lymphoma

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

Trial Summary

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 data supports the effectiveness of the treatment Donor-Derived EBV-Specific T Cells for lymphoma?

Research shows that using EBV-specific T cells, which are immune cells trained to target the Epstein-Barr virus, can effectively treat and prevent EBV-related lymphomas, especially in patients with weakened immune systems. In several studies, patients receiving these T cells showed significant improvement, with many achieving complete remission of their disease. ^{1 2 3 4 5}

Is T Cell Therapy for Lymphoma safe for humans?

Research shows that T Cell Therapy, including EBV-specific T cells, is generally safe for humans. Studies have reported no immediate infusion-related toxic effects and only rare cases of complications, suggesting it is well-tolerated in patients. ^{1 2 4 6 7}

What makes the treatment with Donor-Derived EBV-Specific T Cells unique for lymphoma?

This treatment is unique because it uses T cells (a type of immune cell) specifically trained to target the Epstein-Barr virus (EBV), which is linked to certain lymphomas. Unlike standard treatments, it involves infusing these specialized cells from a donor to help the patient's immune system fight the virus and prevent or treat lymphoma, especially in patients who have undergone bone marrow transplants. ^{2 3 4 5 8}

What is the purpose of this trial?

Single-patient trial aiming to provide immunological consolidation following allogeneic stem cell transplantation to a young adult patient suffering from a systemic EBV-positive lymphoma of childhood.

Eligibility Criteria

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

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

Treatment Details

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

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

Adoptive immunotherapy for Epstein-Barr virus-related lymphoma. [2019]

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

Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors. [2023]

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

Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. [2021]

4. United States 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. [2021]

5. United States 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. [2019]

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

EBV/LMP-specific T cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation. [2022]

7. United States 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Virus-specific T-cell banks for 'off the shelf' adoptive therapy of refractory infections. [2018]