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

Trial Summary

What is the purpose of this trial?

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 (cHL) (hereafter these 3 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study. In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins. The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients

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.

What data supports the effectiveness of the treatment CD30.CAR-EBVST cells for lymphoma?

Research shows that CD30-targeted CAR T-cell therapy has been effective in treating relapsed or refractory CD30+ lymphomas, with a high overall response rate and some patients achieving complete remission. Additionally, combining this therapy with anti-PD-1 antibodies has further improved its effectiveness, with minimal side effects. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy, including those targeting CD30, has shown a good safety profile in some studies, with no serious adverse events directly attributed to the treatment. However, it can cause side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), which need careful management. ^{3 6 7 8 9}

What makes the CD30.CAR-EBVST cell treatment unique for lymphoma?

The CD30.CAR-EBVST cell treatment is unique because it uses engineered T cells to specifically target the CD30 protein found on lymphoma cells, while sparing healthy cells, which helps reduce side effects. This approach is different from traditional therapies as it combines the targeting of CD30 with Epstein-Barr Virus-specific T cells to enhance the immune response against the cancer. ^{1 2 3 4 10}

Research Team

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

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]

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 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]

References

1. 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]

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

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. [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. Netherlands pubmed.ncbi.nlm.nih.gov

Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. [2023]

5. Switzerland 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. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. [2022]

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

Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

9. England pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. [2021]

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

Chimeric Antigen Receptor-Engineered T Cell Therapy in Lymphoma. [2020]