CD30 CAR T-Cells for Lymphoma

(CARCD30 Trial)

Not currently recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids, others

Disqualifiers: 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 tests a new treatment for certain types of lymphoma, a cancer of the lymphatic system. The treatment combines antibodies (proteins that protect the body) with T cells (blood cells that fight infections) to create a powerful cell capable of recognizing and killing lymphoma cells more effectively. Researchers aim for these modified T cells, known as autologous CAR.CD30 EBV specific-CTLs, to last longer in the body and improve the chances of fighting the cancer. Individuals with CD30-positive lymphoma and past Epstein-Barr virus exposure might be suitable for this trial if they have faced challenges with standard therapies. 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 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 cannot be on systemic corticosteroids or have received certain treatments like anti-CD30 antibody-based therapy or investigational agents within the past six weeks.

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

Research has shown that T cells trained to recognize the EBV virus can remain in the bloodstream for many years. These durable T cells are being used to develop a new lymphoma treatment by adding a specific antibody, resulting in CD30 chimeric receptor EBV CTLs.

Previous studies with similar T cell therapies have shown mixed results. Anti-CD30 CAR T cells, part of this new treatment, have sometimes caused serious side effects like rashes and prolonged low blood cell counts. However, these therapies have successfully treated cancers without the severe long-term side effects associated with some traditional cancer treatments.

The current study is in its early stages, with safety information still being collected. Early-stage trials typically focus on safety and determining the right dose. While there have been successes, the safety profile for this specific treatment is still being established. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the autologous CAR.CD30 EBV specific-CTLs treatment for lymphoma because it harnesses the body's own immune system in a novel way. Unlike traditional therapies like chemotherapy and radiation, which can damage healthy cells, this treatment uses genetically modified T-cells to specifically target and destroy cancer cells expressing the CD30 protein. This targeted approach not only promises to be more effective but could also result in fewer side effects, offering a more personalized and potentially safer treatment option for lymphoma patients.

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

Research has shown that modifying T cells to find and attack lymphoma cells holds promise. In this trial, participants will receive autologous CAR.CD30 EBV specific-CTLs, where T cells are altered to include a new gene that enhances their ability to recognize cancer cells. Studies have demonstrated significant improvements in patients with CD30-expressing lymphomas using this method. However, results have varied, with some patients experiencing only short-term benefits. By combining this method with EBV-specific T cells, which remain in the bloodstream longer, scientists aim to extend the treatment's duration. Although promising, the potential for long-lasting effects continues to be studied. ^{1 5 6 7 8}

Who Is on the Research Team?

Helen E Heslop, MD

Principal Investigator

Baylor College of Medicine/Center for Cell and Gene Therapy

Are You a Good Fit for This Trial?

This trial is for children and adults with relapsed CD30+ Hodgkin's or Non-Hodgkin's Lymphoma, or those who can't complete standard therapy. Participants must be EBV positive, not pregnant, willing to use effective birth control, have a certain level of blood oxygenation and organ function, and sign informed consent.

Inclusion Criteria

Hgb > 8.0

AST 3 times or less than upper limit of normal.

Bilirubin 1.5 times or less than upper limit of normal.

Exclusion Criteria

Pregnant or lactating.

I'm sorry, but I need more specific information about the treatment exclusion criteria in order to provide a simplified explanation. Could you please provide more details?

Currently receiving any investigational agents or received any tumor vaccines within the previous six weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of autologous EBV-specific cytotoxic T-lymphocytes (CTLs) genetically modified to express an artificial T-cell receptor (CAR) targeting the CD30 molecule

6 weeks

1 visit (in-person) at Day 0 for cell infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Long-term follow-up

Participants are followed for long-term side effects of gene transfer

15 years

What Are the Treatments Tested in This Trial?

Interventions

• autologous CAR.CD30 EBV specific-CTLs

Trial Overview The study tests genetically modified T cells that target lymphoma by combining an anti-CD30 antibody with EBV-specific T cells. This aims to create long-lasting 'chimeric receptor' T cells capable of recognizing and killing lymphoma more effectively than previous treatments.

How Is the Trial Designed?

Group I: autologous CAR.CD30 EBV specific-CTLs Experimental Treatment 1 Intervention

Group One Dose (CTLs CAR.CD30) at Day 0: 2x10\^7 cells/m2 Group Two Dose (CTLs CAR.CD30) at Day 0: 5x10\^7 cells/m2 Group Three Dose (CTLs CAR.CD30) at Day 0: 1x10\^8 cells/m2

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

The study developed a novel CD30-chimeric antigen receptor (CAR) T cell therapy using memory stem T cells (TSCM), which showed improved persistence and antitumor activity against Hodgkin lymphoma in mouse models.

CD30-CAR TSCM-like cells effectively eradicated Hodgkin lymphoma tumors in vivo, demonstrating a survival advantage and enhanced tumor infiltration compared to more differentiated CAR T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory stem T cells modified with a redesigned CD30-chimeric antigen receptor show an enhanced antitumor effect in Hodgkin lymphoma. Alvarez-Fernández, C., Escribà-Garcia, L., Caballero, AC., et al.[2022]

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]

CAR T cells targeting CD30 show promise in treating lymphoma without depleting healthy B cells, as they do not attack CD30(+) hematopoietic stem and progenitor cells (HSPCs).

The study demonstrated that anti-CD30 CAR T cells maintain normal blood cell levels in humanized mice, indicating a safer therapeutic profile compared to CD19-targeting CAR T cells, which can lead to lasting depletion of healthy B cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior Therapeutic Index in Lymphoma Therapy: CD30(+) CD34(+) Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack. Hombach, AA., Görgens, A., Chmielewski, M., et al.[2018]

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]

The study demonstrates that CD30-targeted CAR-T cell therapy is effective in treating recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL), showing significant tumor suppression in both laboratory and mouse model experiments.

The engineered 9C11-2 CAR T cells exhibited strong cytotoxic effects against CD30-positive cancer cells, indicating their potential as a promising therapeutic option for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb. Wu, Y., Chen, D., Lu, Y., et al.[2022]

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]

Third-generation anti-CD30 CAR T-cells (CD28BBz) show long-term persistence and strong anti-tumor activity in models of Hodgkin lymphoma and anaplastic large cell lymphoma, outperforming second-generation CAR T-cells (CD28z).

These CAR T-cells are well tolerated with minimal side effects, indicating they are a safe and effective treatment option for patients with Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity. Zhang, S., Gu, C., Huang, L., et al.[2022]

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11223124/

Rejection resistant CD30.CAR-modified Epstein-Barr virus ... CAR EBVSTs have the potential to be an effective OTS therapy against CD30+ tumors and, if successful, could then be used as a platform to target other tumor ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01192464

EBV CTLs Expressing CD30 Chimeric Receptors For CD ... Both antibodies and T cells have been used to treat patients with cancers: they both have been shown promise, but have not been strong enough to cure most ...

3. ashpublications.org ashpublications.org/bloodadvances/article/8/3/802/498655/Transient-responses-and-significant-toxicities-of

Transient responses and significant toxicities of anti-CD30 ... Anti-CD30 CAR T cells had low efficacy in patients with CD30-expressing lymphoma. Rashes and prolonged cytopenias were frequent and severe in some cases ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S247395292100690X

Adoptive T-cell therapy for Hodgkin lymphoma Adoptive T-cell therapy with Epstein-Barr virus–specific cytotoxic T lymphocytes and CD30 CAR T cells have demonstrated significant clinical ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7655020/

Anti-CD30 CAR-T Cell Therapy in Relapsed and ... Sustained complete responses in patients with lymphoma receiving autologous cytotoxic T lymphocytes targeting Epstein-Barr virus latent membrane proteins.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1988944/

Epstein Barr virus–specific cytotoxic T lymphocytes expressing ... These CD30CAR+ CTLs killed both autologous EBV+ cells through their native receptor and EBV−/CD30+ targets through their major histocompatibility complex (MHC)– ...

7. cell.com cell.com/molecular-therapy-family/oncology/fulltext/S2950-3299(24)00056-0

Rejection resistant CD30.CAR-modified Epstein-Barr virus- ... Autologous T cells have had remarkable success in treating cancers and lack the severe long-term toxicities associated with conventional ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1465324923000993

Epstein‒Barr virus–associated cellular immunotherapy This review will mainly focus on discussing EBV-specific cytotoxic T lymphocytes and will touch on therapeutic EBV vaccines and chimeric antigen receptor T- ...