Cell Therapy for Hodgkin's Lymphoma

Overseen By Catherine Cheng

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Disqualifiers: Major surgery, Investigational agents, Chemotherapy, others

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

Compensation: Varies

Number of Visits: Unknown

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy, ATLCAR.CD30.CCR4, for people with Hodgkin's Lymphoma, a type of cancer. Researchers aim to determine the right dose and assess its safety. They hope this treatment can reduce long-term effects and lower the risk of mortality from the disease. Individuals diagnosed with Classical Hodgkin Lymphoma may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, it offers participants the opportunity to be among the first to receive this treatment and help evaluate its effectiveness in an initial group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, you can receive standard-of-care treatments like chemotherapy or radiation during certain parts of the trial, as long as your doctor thinks it's best for you.

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

Research shows that ATLCAR.CD30.CCR4, a type of CAR-T cell therapy, is under study for treating Hodgkin's Lymphoma. This treatment targets CD30, a common feature on Hodgkin's Lymphoma cells.

Regarding safety, studies have found that ATLCAR.CD30.CCR4 is generally well-tolerated by patients. However, like many treatments, it can cause side effects. Some patients have experienced neurotoxicity, which affects the nervous system. Researchers carefully monitor these effects during the trial.

While this treatment remains under testing, its presence in early clinical trials means that safety is still under assessment. Those considering participation should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ATLCAR.CD30.CCR4 is unique because it uses a groundbreaking approach called cell therapy to target Hodgkin's Lymphoma. Unlike traditional treatments that rely on chemotherapy or radiation, this therapy modifies the patient's own immune cells to specifically attack cancer cells. Researchers are excited because it has the potential to offer more precise treatment with fewer side effects, and it represents a significant step forward in personalized cancer care. Additionally, its ability to be combined with standard-of-care bridging therapies adds flexibility in patient management.

What evidence suggests that ATLCAR.CD30.CCR4 could be an effective treatment for Hodgkin's Lymphoma?

Research has shown that using CAR-T cells to target CD30 holds promise for treating Hodgkin's Lymphoma. In this trial, participants will receive ATLCAR.CD30.CCR4 cells, which combine T cells with antibodies to specifically attack and destroy cancer cells with the CD30 marker. Studies have found high success rates, with some patients experiencing long-lasting improvements. Early research supports this method, suggesting it could offer a new option for patients who haven't responded to other treatments. While more information is needed, the initial results are hopeful for this therapy. ^{1 2 5 6 7}

Who Is on the Research Team?

Natalie S. Grover

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Classical Hodgkin Lymphoma, who have a Karnofsky score above 60%, indicating they can care for themselves. They must consent to the study and allow their health information to be used. Patients already receiving standard treatments like chemotherapy or radiation may still qualify.

Inclusion Criteria

I can receive standard treatments to manage my condition until the study treatment starts.

I have been diagnosed with Classical Hodgkin Lymphoma.

Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study. As these criteria are unchanging they will be evaluated at the time of initial enrollment and not continuously throughout the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Manufacturing and Bridging Therapy

Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells and receive standard-of-care bridging therapy during this period

Variable

Lymphodepletion and Cell Infusion

Subjects undergo lymphodepletion followed by infusion of ATLCAR.CD30.CCR4 cells

2-14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years

What Are the Treatments Tested in This Trial?

Interventions

• ATLCAR.CD30.CCR4
• Chemotherapy

Trial Overview The trial tests ATLCAR.CD30.CCR4 cells in patients with Hodgkin's Lymphoma. It's an early-phase study determining safe dosage levels and how well these cells work as treatment. Participants will receive cell infusions after a preparatory 'lymphodepletion' process, followed by long-term monitoring.

How Is the Trial Designed?

Group I: ATLCAR.CD30 Experimental Treatment 2 Interventions

Subjects will be enrolled on 1 of 3 dose levels as determined by a 3+3 design. Up to 25 evaluable subjects may then be enrolled in the phase II portion of the study. Subjects may have cells procured to manufacture the ATLCAR.CD30.CCR4 cells if they meet eligibility for procurement. During the time period necessary to manufacture the ATLCAR.CD30.CCR4 cells, Subjects will be allowed to receive standard-of-care bridging therapy at the discretion of their local oncologist. Prior to cell infusion, subjects will undergo additional eligibility evaluations, and then if eligible, will undergo lymphodepletion followed by cell infusion 2-14 days later. Subjects will then be followed for 15 years as is required for studies involving gene transfer experiments

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

CD30-directed CAR-T cells show promise as a treatment for relapsed or refractory lymphomas, particularly classical Hodgkin lymphoma, with early clinical trials indicating minimal toxicity and some preliminary efficacy.

Enhancing the persistence and expansion of CAR-T cells is crucial for improving treatment outcomes, with ongoing research focusing on optimizing treatment regimens and combining therapies to boost effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges of driving CD30-directed CAR-T cells to the clinic. Grover, NS., Savoldo, B.[2020]

Hodgkin lymphoma (HL) has a high cure rate of nearly 70% with initial chemotherapy, but about 50% of patients relapse after autologous hematopoietic cell transplantation (auto-HCT), indicating a need for better treatment options for this subgroup.

Emerging treatments like chimeric antigen receptor T-cell therapy targeting CD30 show promising safety and efficacy in early clinical trials for patients with relapsed or refractory HL, offering hope for potentially curative options after auto-HCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapse of Hodgkin lymphoma after autologous hematopoietic cell transplantation: A current management perspective. Iqbal, M., Kharfan-Dabaja, MA.[2021]

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]

The study highlights that Hodgkin lymphoma cells produce specific chemokines (TARC/CCL17 and MDC/CCL22) that attract regulatory T cells, creating an immunosuppressive environment that hinders effector CD8(+) T cell activity.

By engineering effector T cells to express the CCR4 receptor, researchers improved their ability to migrate to Hodgkin lymphoma cells, enhancing their tumor-fighting capabilities and leading to better tumor control in mouse models, suggesting a promising strategy for treating patients with Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Di Stasi, A., De Angelis, B., Rooney, CM., et al.[2023]

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]

Chimeric antigen receptor (CAR)-transduced T cells targeting CD30 have shown to be safe and effective in treating Hodgkin lymphoma (HL).

The review also highlights the challenges and ongoing trials of using CAR-T cells targeting CD5 and CD7 in T-cell lymphomas (TCL), indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells in Hodgkin and T-Cell Lymphomas. Muhsen, IN., Hill, LC., Ramos, CA.[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]

In a phase I study involving 9 patients with relapsed/refractory Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL), CD30-targeted CAR T-cell therapy was found to be safe, with no observed toxicities related to the treatment.

The therapy resulted in significant clinical responses, including complete responses in 2 patients and stable disease in several others, suggesting that CD30.CAR-Ts could be an effective treatment option for these lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. Ramos, CA., Ballard, B., Zhang, H., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03602157

NCT03602157 | Study of CAR-T Cells Expressing CD30 ... This study will combine both T cells and antibodies in order to create a more effective treatment called Autologous T Lymphocyte Chimeric Antigen Receptor cells ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2018-01904

ATLCAR.CD30.CCR4 with or without ... ATLCAR.CD30.CCR4 with or without autologous CD30CAR-CD28-CD3zeta-expressing T-Lymphocytes (ATLCAR.CD30) works in treating patients with CD30+ Hodgkin lymphoma.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10697615/

CAR-T cells in Hodgkin and T-cell lymphomas - PMC Herein, we review published data on clinical trials using CAR-T cells for HL and TCL. We will begin by summarizing the results of targeting CD30 via CAR-T cells ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121027324

CD30-Directed CAR-T Cells Co-Expressing CCR4 in ... Chimeric antigen receptor T cells targeting CD30 (CD30.CAR-T) have shown high response rates, including some durable remissions, in patients ...

5. ashpublications.org ashpublications.org/bloodadvances/article/8/3/799/514908/CARs-for-Hodgkin-engine-fine-tuning-is-in-order

CARs for Hodgkin: engine fine-tuning is in order CARTs targeting CD19 and B-cell maturation antigen have demonstrated impressive efficacy in B-cell non-Hodgkin lymphomas (NHLs) and multiple ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/919/530888/CD30-CAR-T-Cells-Co-Expressing-the-CCR4-Chemokine

CD30.CAR-T Cells Co-Expressing the CCR4 Chemokine ... CAR-Ts) are efficacious in treating patients (pts) with relapsed/refractory (r/r) classical Hodgkin lymphoma (HL), but many pts relapse after ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06090864

Study Details | NCT06090864 | ATLCAR.CD30.CCR4 for ... Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria related to the administration of ATLCAR.