T-cell Therapy for Lymphoma

(ATECRAB Trial)

Not currently recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Disqualifiers: Pregnancy, HIV, HBV, HCV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using T cells, a type of immune cell, to combat non-Hodgkin Lymphoma or chronic Lymphocytic Leukemia when standard treatments fail. The approach combines T cells with a modified antibody that targets lymphoma cells, enhancing the body's ability to fight cancer. Researchers aim to determine the safest dose and assess the duration of the treatment's effects. This trial may suit those with recurring lymphoma or CLL who have a CD19-positive tumor and have recovered from recent chemotherapy. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 must not be on any investigational agents or have received tumor vaccines in the past six weeks, and you cannot have been treated with rituximab in the past eight weeks.

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

Research has shown that treatments using T cells, like those in this trial, have potential in fighting lymphoma, a type of cancer affecting the lymph glands. One study found that using Epstein-Barr Virus (EBV)-specific T cells in patients was safe. These T cells can help manage certain diseases without major safety concerns.

Another study suggested that these T cells can remain active in the body for a long time, which is promising for long-term treatment. Importantly, findings from trials on these T cells showed that they do not cause major side effects in patients.

While this specific treatment is not yet approved by the FDA, similar T cell treatments have generally been well-tolerated. This trial aims to determine the best dose that is both safe and effective. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they represent a novel approach to fighting lymphoma. Unlike standard treatments like chemotherapy and radiation, which attack cancer cells broadly, this therapy leverages the body's own immune system. It involves engineering T-cells, a type of white blood cell, to specifically target and destroy lymphoma cells using a chimeric receptor. This targeted method could potentially lead to more effective outcomes with fewer side effects. Additionally, the use of autologous or syngeneic cells means that the treatment is personalized, reducing the risk of rejection and enhancing compatibility.

What evidence suggests that this treatment might be an effective treatment for lymphoma?

Research has shown that CAR T-cell therapy holds promise for individuals with lymphoma and chronic lymphocytic leukemia (CLL). This therapy uses specially modified T-cells to locate and destroy cancer cells by attaching to a protein called CD19 on these cells. Specifically, anti-CD19 CAR T-cell therapy has proven effective for patients with recurrent or hard-to-treat B-cell lymphomas. Many patients have experienced significant tumor reduction following this treatment. In this trial, participants will receive autologous or syngeneic PBTLs and EBV-CTLs, which include CD19-CD28 chimeric receptor T cells. Combining T-cells with the protein CD28 helps them remain active longer, potentially enhancing their cancer-fighting ability. Although further research is necessary, early results offer hope for those facing these challenging cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for people with certain types of blood cancers like non-Hodgkin Lymphoma or chronic Lymphocytic Leukemia that have returned or persisted despite treatment. Participants must be over the worst side effects of past treatments, not on other experimental drugs, and without severe liver, heart, or kidney issues. They should also not be pregnant, free from serious infections like HIV/HBV/HCV/CMV, and willing to use effective birth control.

Inclusion Criteria

I haven't received rituximab in the last 8 weeks.

I have recurring low or intermediate grade B-cell lymphoma or B-CLL, or I can't complete standard therapy.

I am not currently on experimental drugs or had cancer vaccines in the last 6 weeks.

Exclusion Criteria

History of hypersensitivity reactions to murine protein-containing products

I do not have an active infection with HIV, hepatitis B, hepatitis C, or CMV.

My tumor is located where it could block my airway if it grows.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of CD19-CD28 chimeric receptor T cells and CD19 chimeric receptor-EBV specific T cells, with possible cyclophosphamide pre-treatment

6 weeks

1 visit (in-person) for infusion, followed by clinic visits for monitoring

Evaluation

Evaluation period to assess benefit from treatment, with potential for additional doses if beneficial

4-6 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including long-term follow-up for gene transfer side effects

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous or Syngeneic PBTLs and EBV-CTLs

Trial Overview The study tests T cells modified with an anti-CD19 antibody (chimeric receptor-T cells) and a protein CD28 to make them more active against cancer. It also uses T cells trained to fight Epstein-Barr Virus (EBV). The goal is to find the highest safe dose of these chimeric T cells, understand their longevity in the body and side effects, and see if they help treat lymphoma or CLL.

How Is the Trial Designed?

Group I: autologous or syngeneic PBTLs and EBV-CTLs Experimental Treatment 1 Intervention

The subject will be assigned a dose of CD19-CD28 chimeric receptor T cells at study entry.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

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]

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]

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 114 patients receiving EBV-specific cytotoxic T lymphocyte (CTL) infusions, the treatment showed minimal toxicity and effectively prevented EBV-related lymphoproliferative disease (LPD), with no cases in the 101 patients who received prophylaxis.

Among the 13 patients treated for existing LPD, 11 achieved sustained complete remissions, demonstrating the efficacy of CTLs in treating this condition, with functional CTLs persisting for up to 9 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Heslop, HE., Slobod, KS., Pule, MA., et al.[2023]

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]

Antigen-specific cytotoxic T lymphocytes (CTLs) generated from induced pluripotent stem cells show rejuvenated function and strong antitumor effects against Epstein-Barr virus (EBV)-associated lymphomas, which are common in Asia and have a poor prognosis.

The study developed allogeneic EBV-specific CTLs for potential 'off-the-shelf' therapy, making it feasible for clinical use in treating these lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Induced pluripotent stem cell-derived rejuvenated cytotoxic T lymphocyte therapy for Epstein-Barr virus-associated lymphomas: application to clinical practice]. Ando, M.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11554992/

Clinical outcomes of chimeric antigen receptor T-cell therapy ... Clinical outcomes of chimeric antigen receptor T-cell therapy following autologous hematopoietic stem cell transplantation in 38 patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9886865/

Efficacy of chimeric antigen receptor T cell therapy and ... We aimed to compare the efficacy of chimeric antigen receptor T (CAR-T) cell therapy with that of autologous stem cell transplantation (auto-HSCT) in ...

3. mdpi.com mdpi.com/2673-6357/6/1/3

Real-World Outcomes of Anti-CD19 Chimeric Antigen ... Anti-CD19 CAR T-cell therapy works by targeting the CD19 receptor on malignant and non-malignant B-cells to allow for identification and destruction of lymphoma ...

4. haematologica.org haematologica.org/article/view/haematol.2024.285613

Outcomes of patients with primary central nervous system ... Outcomes of patients with primary central nervous system lymphoma following CD19-targeted chimeric antigen receptor T-cell therapy

5. astctjournal.org astctjournal.org/article/S2666-6367(25)00639-6/fulltext

Outcomes of Outpatient CD19-Targeted Chimeric Antigen ... Outcomes of outpatient CD19-targeted chimeric antigen receptor T-cell therapy in relapsed or refractory B-cell lymphomas: a systematic review and meta-analysis.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2817637/

Long-term outcome of EBV-specific T-cell infusions to prevent ... We conclude that the CTL lines described here provide safe and effective prophylaxis or treatment for lymphoproliferative disease in transplantation recipients.

7. 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.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1895521/

Treatment of solid organ transplant recipients with ... We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)–specific cytotoxic T lymphocytes (CTLs) for the ...

9. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2780407

Comparison of Allogeneic Stem Cell Transplant and ... These findings suggest that allogeneic HSCT may have better effectiveness but be less safe than autologous HSCT for patients with refractory or relapsed ...

10. link.springer.com link.springer.com/article/10.1007/s00277-023-05416-x

Autologous hematopoietic stem cell transplantation ... Autologous hematopoietic stem cell transplantation improves survival outcomes in peripheral T-cell lymphomas: a multicenter retrospective real- ...