CD30 CAR T-Cells for Lymphoma

(CARCD30 Trial)

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

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins the protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. 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 patients. This study combines the two methods. We have found from previous research that we can put a new gene into T cells that will make them recognize cancer cells and kill them. We now want to see if we can attach a new gene to T cells that will help them do a better job at recognizing and killing lymphoma cells. The new gene we will put in T cells makes an antibody called anti-CD30. The antibody alone has not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T cells seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown. We have found that T cells that are also trained to recognize the EBV virus (that causes infectious mononucleosis) can stay in the blood stream for many years. These are called EBV specific Cytotoxic T Lymphocytes. By joining the anti-CD30 antibody to the EBV CTLs, we believe that we will also be able to make a cell that can last a long time in the body and recognize and kill lymphoma cells. We call the final cells CD30 chimeric receptor EBV CTLs. T We hope that these new cells may be able to work longer and target and kill lymphoma cells. However, we do not know that yet.

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.

What data supports the effectiveness of the CD30 CAR T-Cells treatment for lymphoma?

Research shows that CD30 CAR T-Cells can effectively target and kill lymphoma cells that express the CD30 molecule, which is common in Hodgkin lymphoma. These cells have been shown to persist in the body and produce antitumor effects, even in cases where the tumor does not express the Epstein Barr virus (EBV) antigens, making them a promising treatment option. ^{1 2 3 4 5}

Is CD30 CAR T-cell therapy safe for humans?

CD30 CAR T-cell therapy has been shown to be generally safe in humans, with minimal side effects such as localized swelling at treatment sites. Studies have demonstrated its safety in treating conditions like Hodgkin lymphoma and EBV-related lymphomas, with no major complications reported. ^{1 2 6 7 8}

How is the CD30 CAR T-Cell treatment for lymphoma different from other treatments?

This treatment is unique because it uses specially modified immune cells (CAR T-cells) that are designed to target and kill lymphoma cells expressing a protein called CD30, while sparing healthy cells. It combines the ability to target both EBV-positive and CD30-positive cancer cells, offering a more precise approach compared to traditional therapies. ^{1 2 3 9 10}

Research Team

Helen E Heslop, MD

Principal Investigator

Baylor College of Medicine/Center for Cell and Gene Therapy

Eligibility Criteria

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

AST 3 times or less than upper limit of normal.

Hgb > 8.0

Bilirubin 1.5 times or less than upper limit of normal.

Exclusion Criteria

Pregnant or lactating.

I do not have an active infection with HIV, HTLV, HBV, or HCV.

I have received rituximab within the last 4 months or my CD19+ B cells are at least 2%.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

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

Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30zeta artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. [2021]

2. Japan 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]. [2022]

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

Superior Therapeutic Index in Lymphoma Therapy: CD30(+) CD34(+) Hematopoietic Stem Cells Resist a Chimeric Antigen Receptor T-cell Attack. [2018]

4. Australia 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. [2022]

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

CARs and cancers: questions and answers. [2021]

6. United States 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for patients with refractory EBV-related lymphoma. [2020]

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

The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity. [2022]

9. England 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. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

T cell therapies. [2019]