TGFbeta-resistant Immune Cells for Lymphoma

(TGF-beta Trial)

Not currently recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Disqualifiers: Severe infection, GVHD, HIV, pregnancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks for initial treatment, with potential extension

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals whose lymphoma (a type of lymph gland cancer) has returned or did not respond to treatment. The treatment uses special immune cells, known as TGFbeta resistant LMP-specific CTLs, designed to target cancer cells often linked to the Epstein Barr virus (EBV). Researchers aim to determine if these modified cells can survive better and effectively attack the tumor. This trial is for patients with EBV-positive lymphoma that is difficult to treat or has recurred, and who have undergone previous treatments, including stem cell transplants. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must have been off other investigational therapies for one month before joining the study.

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

Research shows that a new type of immune cell therapy is undergoing testing for certain types of lymphoma, a blood cancer. These specially designed immune cells target and destroy cancer cells. However, researchers continue to gather safety information.

In previous studies, similar T-cell therapies have treated other cancers, such as those occurring after a transplant. Some patients experienced a partial response, where their cancer reduced in size but did not disappear completely. The new therapy represents an experimental advancement, aiming to improve treatment by overcoming a substance produced by cancer cells that helps them evade the immune system.

As this is an early-stage study, the primary goal is to identify the safest dose and understand potential side effects. The treatment has not yet received FDA approval, so researchers are still assessing its safety in humans. This trial will help determine the most effective way to use these special immune cells to combat lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TGFbeta-resistant LMP-specific CTLs for lymphoma because they offer a novel approach by harnessing the power of the immune system. Unlike traditional therapies like chemotherapy and radiation, which attack cancer cells but also harm healthy cells, these CTLs are designed to specifically target cancer cells by resisting the immunosuppressive effects of TGFbeta, a protein that typically helps tumors evade immune detection. This targeted action not only has the potential to be more effective but also may result in fewer side effects, making it a promising option for patients.

What evidence suggests that TGFbeta resistant LMP-specific CTLs might be an effective treatment for Lymphoma?

Research has shown that a new type of immune cell therapy, TGFbeta-resistant LMP-specific CTLs, might help treat lymphoma. These specially engineered T cells, which participants in this trial will receive, have been tested in patients with Hodgkin lymphoma and demonstrated the ability to grow and remain active safely. They resist a substance called TGFbeta, which cancer cells use to evade the immune system, allowing immune cells to attack the cancer more effectively. While earlier versions of this therapy had limited success, adding a TGFbeta resistance gene aims to improve outcomes. Early results suggest this could enhance the treatment's effectiveness for lymphoma that has returned after previous treatment. ^{1 3 5 6 7}

Who Is on the Research Team?

Helen E Heslop, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with EBV-positive lymphoma or lymphoepithelioma, regardless of age or sex. They should have a life expectancy of at least 6 weeks post-CTL infusion, be able to perform daily activities (Karnofsky score ≥50), and have certain levels of blood and liver function. It's not for those with severe infections, significant GVHD after transplant, HIV positive status, or pregnant women.

Inclusion Criteria

Patients with bilirubin 3x normal or less, AST 5x normal or less, and Hgb greater than 8.0

Patients with life expectancy 6 weeks or greater from the time of CTL infusion.

Patients should have been off other investigational therapy for one month prior to entry in this study.

Exclusion Criteria

I am not pregnant and understand the need for contraception during the study.

HIV positive at time of procurement cells for CTL generation

I do not have a severe ongoing infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TGFb-resistant LMP-specific CTLs with initial two doses given two weeks apart, followed by up to six additional doses if beneficial

6 weeks for initial treatment, with potential extension

2 visits for initial doses, up to 6 additional visits for extended treatment

Follow-up

Participants are monitored for safety, effectiveness, and long-term outcomes after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• TGFbeta resistant LMP-specific CTLs

Trial Overview The study tests TGFbeta-resistant LMP-specific CTLs in patients whose lymphoma has returned or persisted despite treatment. The goal is to find the highest safe dose, understand side effects, and see if this gene-modified therapy can fight cancer by targeting EBV-infected cells that evade the immune system.

How Is the Trial Designed?

Group I: TGFbeta resistant LMP-specific CTLs Experimental Treatment 1 Intervention

CTLs be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. If patients with active disease have stable disease or a partial response at their 6 week or subsequent evaluations they will be eligible to receive up to 6 additional doses of CTLs at 1-2 monthly intervals-each of which will consist of the same cell number as their second injection.

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

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00368082

Autologous/Allogeneic TGFbeta-resistant LMP-specific ... The purpose of this study is to find the largest safe dose of TGFb resistant LMP-specific CTLs, to learn what the side effects are and to see whether this ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5891126/

Tumor-Specific T-Cells Engineered to ... - PubMed Central Conclusion. TGF-β–resistant tumor-specific T cells safely expand and persist in patients with Hodgkin lymphoma without lymphodepleting chemotherapy before ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7796313/

Therapeutic targeting of TGF-β in cancer: hacking a master ... The inhibition of TGF-β activity is a promising approach to increase the efficacy of T cell checkpoint blockade therapies.

4. clinicaltrial.be clinicaltrial.be/en/details/13695?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Autologous/Allogeneic TGFbeta-resistant LMP-specific ... If after the second infusion, there is a reduction in the size of the subject's lymphoma (or no increase) on CT or MRI scans as assessed by a ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2212137423000465

Targeting transforming growth factor beta signaling in ... Specifically, the clinical outcome for metastatic osteosarcoma remains poor; less than 30 % of patients who exhibit metastases will survive five years after the ...

6. withpower.com withpower.com/trial/phase-1-lymphoma-3-2006-a4881

TGFbeta-resistant Immune Cells for Lymphoma (TGF-beta ... Trial Overview The study tests TGFbeta-resistant LMP-specific CTLs in patients whose lymphoma has returned or persisted despite treatment. The goal is to find ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10666000/

Targeting transforming growth factor beta signaling in ... TGF-β antagonists have been shown to have effects on osteosarcoma in vitro and in vivo. One of the small molecule TβRI inhibitors, Vactosertib, is currently ...