CAR T-cell Therapy for Lymphoma

Recruiting at 1 trial location

Overseen By Carlos Ramos, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids, others

Disqualifiers: Pregnancy, Cardiac disease, Infections, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 1 day

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment using special T cells from healthy donors to target lymphoma, including diffuse large B cell lymphoma, NK and T cell lymphomas, and classical Hodgkin lymphoma. The focus is on patients whose cancer has returned or hasn't fully responded to standard treatments. Researchers aim to find the safest dose and determine if these T cells, which can recognize a virus linked to some lymphoma cells, can help fight the cancer. Individuals with lymphoma featuring CD30-positive tumors who have already tried other treatments might be a good fit for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance 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 if you need to stop taking your current medications. However, you cannot participate if you are currently using systemic corticosteroids at a dose higher than 10 mg/day of prednisone or if you have received certain treatments recently, like investigational drugs or specific chemotherapy.

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

Research shows that CD30.CAR-EBVST cells, specially modified immune cells from healthy donors, have potential in treating patients with CD30-positive lymphoma. Studies indicate that this therapy is generally safe and effective, with most patients tolerating it well. Some patients have shown positive responses to the treatment.

Although still under investigation, earlier studies aimed to find the highest safe dose by testing different amounts to avoid severe side effects. So far, results suggest that the treatment is manageable for patients. However, as this research remains in the early stages, the study will continue to monitor any side effects to ensure safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for lymphoma, which typically involves chemotherapy or radiation, CD30.CAR-EBVST cells are a type of CAR T-cell therapy that offers a more targeted approach. This treatment uses genetically modified T-cells designed to specifically recognize and attack cancer cells expressing the CD30 protein, a marker often found in lymphoma cases. Researchers are excited about this therapy because it has the potential to directly engage and destroy cancer cells, potentially leading to fewer side effects and more effective outcomes compared to conventional treatments.

What evidence suggests that CD30.CAR-EBVST cells might be an effective treatment for lymphoma?

Studies have shown that CD30.CAR-EBVST cells can help treat certain types of lymphoma. In earlier research, about half of the patients with lymphoma containing the Epstein-Barr virus (EBV) in their cancer cells responded well to this therapy. In this trial, participants will receive CD30.CAR-EBVST cells, which are specially designed to find and attack cancer cells with both EBV and a protein called CD30. Researchers believe this dual-target method improves the chances of successfully eliminating the cancer cells. Early signs suggest this treatment could be a promising new option for patients whose lymphoma hasn't responded to other treatments. ^{2 4 5 6 7}

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 patients aged 12-75 with certain types of lymphoma (Hodgkin's, non-Hodgkin's, or T-cell) that have returned or persisted after treatment. Participants must understand and sign consent, have a Karnofsky/Lansky score over 60%, normal organ function tests, and use effective birth control if sexually active. Those with recent other treatments, hypersensitivity to murine proteins, pregnancy, potential airway obstruction by tumor growth, high-dose steroid use or uncontrolled infections cannot join.

Inclusion Criteria

My kidney function is good.

I have Hodgkin lymphoma.

I have recovered from all major side effects of my previous chemotherapy.

Exclusion Criteria

Pregnant or lactating.

I have severe heart disease that limits my daily activities.

I have received chemotherapy that included gemcitabine in the last 12 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Lymphodepletion Chemotherapy

Participants receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine to prepare for T cell infusion

1 week

1 visit (in-person)

Treatment

Participants receive CD30.CAR-EBVST cell infusion at assigned dose level

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Weekly visits for 8 weeks, then every 3 months for 1 year, then every 6 months for 4 years

What Are the Treatments Tested in This Trial?

Interventions

• CD30.CAR-EBVST cells

Trial Overview The study is testing allogeneic CD30.CAR-EBVST cells from healthy donors on patients whose lymphoma expresses the CD30 protein and may also contain EBV. The goal is to determine the highest safe dose following chemotherapy and assess its effectiveness in treating lymphoma.

How Is the Trial Designed?

Group I: Treatment Phase Experimental Treatment 1 Intervention

Four dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three to six patients will be enrolled at each dose level The dose is based on the number of CD.30 CAR-EBVT-expressing cells administered. The total number of dose levels evaluated will depend upon toxicities experienced. Dose level cohorts will be numbered sequentially. * Dose Level 1: 4 × 10\^7 CD30.CAR-EBVST cells * Dose Level 2: 1 × 10\^8 CD30.CAR-EBVST cells * Dose Level 3: 4 × 10\^8 CD30.CAR-EBVST cells * Dose Level 4: 8 × 10\^8 CD30.CAR-EBVST cells

CD30.CAR-EBVST cells is already approved in United States for the following indications:

Approved in United States as CD30.CAR-EBVSTs for:

• Relapsed or Refractory CD30-Positive Lymphomas
• Classical Hodgkin Lymphoma (cHL)
• Diffuse Large B Cell Lymphoma (DLBCL)
• NK and T Cell Lymphomas (NK/TL)

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

CAR T cell therapy is effective in treating B cell malignancies like acute lymphoblastic leukemia and non-Hodgkin lymphomas, but it can also cause serious side effects, including multi-organ failure.

Early recognition and management of side effects such as cytokine release syndrome and neurotoxicity are crucial for healthcare staff to ensure patient safety during CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. Yáñez, L., Alarcón, A., Sánchez-Escamilla, M., et al.[2021]

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]

CAR T cell therapy targeting CD19 has shown high efficacy in treating relapsed or refractory aggressive B cell non-Hodgkin lymphoma, leading to durable remissions in many patients, as demonstrated in multicenter trials.

The most common side effects of this therapy include cytokine release syndrome and neurotoxicity, highlighting the need for ongoing research to improve safety and explore its use in earlier treatment stages and other types of B cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-Engineered T Cell Therapy in Lymphoma. Strati, P., Neelapu, SS.[2020]

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 phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

In a multi-center phase II clinical trial involving 12 patients with relapsed/refractory CD30+ lymphoma, the combination of anti-CD30 CAR-T therapy and PD-1 inhibitors resulted in a high overall response rate of 91.7%, with 50% of patients achieving complete remission.

The treatment demonstrated minimal toxicity, with only 4 patients experiencing cytokine release syndrome, and no cases of CAR-T-related encephalopathy syndrome, indicating a favorable safety profile alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma. Sang, W., Wang, X., Geng, H., et al.[2022]

In a study of 38 classical Hodgkin's Lymphoma (cHL) specimens, only 5.2% of Reed-Sternberg cells expressed both CD19 and CD30, indicating a limited population eligible for combined CAR T-cell therapy.

A patient treated with low doses of anti-CD19 and CD30 CAR T-cells did not experience severe adverse events and achieved long-term progression-free survival, suggesting that this approach may be safe and effective for high-risk relapsing/refractory cHL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. Xue, Y., Lai, X., Li, R., et al.[2022]

In a study involving 41 heavily pretreated patients with relapsed or refractory Hodgkin lymphoma, CD30-targeted CAR T-cell therapy demonstrated a high overall response rate of 72%, with 59% achieving complete responses after fludarabine-based lymphodepletion.

The therapy showed a favorable safety profile, with most adverse events being grade 3 or higher hematologic issues and only mild cytokine release syndrome observed, indicating that CAR T-cell therapy can be safely extended to treat Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. Ramos, CA., Grover, NS., Beaven, AW., et al.[2022]

CAR-T therapy is an innovative treatment that modifies T cells to target and attack cancer cells, such as those found in large B cell lymphoma.

In this case, a patient treated with CAR-T therapy for lymphoma developed myocarditis, highlighting a potential safety concern associated with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. Lee, DH., Jain, M., Lazaryan, A., et al.[2023]

Adoptive cell therapy (ACT) using CAR-T cells is effective in treating relapsed/refractory hematological malignancies by reprogramming exhausted T cells, targeting specific markers like CD19 and CD20.

However, CAR-T cell therapy can lead to serious adverse events, including cytokine release syndrome and neurotoxicity, which can cause significant immune stress and damage to normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies. Yan, W., Liu, Z., Liu, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04288726

NCT04288726 | Allogeneic CD30.CAR-EBVSTs in Patients ... This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL) or classical Hodgkin lymphoma ...

2. 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 ...

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/allogeneic-anti-cd30-car-epstein-barr-virus-specific-t-lymphocytes?pn=1

Clinical Trials Using Allogeneic Anti-CD30 CAR-Epstein ... NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying allogeneic anti-cd30 car-epstein-barr ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38966037/

Rejection resistant CD30.CAR-modified Epstein-Barr virus ... We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) ...

5. 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- ...

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

Rejection resistant CD30.CAR-modified Epstein-Barr virus- ... CAR-EBVSTs can resist killing by previously primed alloreactive T cells (p-ARTs), we generated EBVST donor-specific p-ARTs by co-culturing PBMCs ...

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/412/491233/CD30-CAR-Modified-Epstein-Barr-Virus-Specific-T

CD30.CAR-Modified Epstein-Barr Virus-Specific T Cells ... CAR-modified Epstein-Barr virus-specific T cells (CD30.CAR EBVSTs) provide a safe and effective off-the-shelf therapy for patients with CD30-positive lymphoma.