CD30 CAR T-Cell Therapy for Lymphoma

Recruiting at 1 trial location

Overseen By Shamina Williams

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Corticosteroids, CYP1A2 inhibitors

Disqualifiers: Pregnancy, HIV, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called ATLCAR.CD30 for individuals with peripheral T-cell lymphoma that has returned or hasn't responded to previous treatments. The treatment uses modified T cells (a type of immune cell) to target and kill cancer cells. Participants will undergo chemotherapy to prepare their bodies before receiving the T-cell therapy. The trial seeks individuals who have tried at least two other treatments for their lymphoma without success. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on certain medications like strong inhibitors of CYP1A2 or systemic corticosteroids at high doses. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that ATLCAR.CD30 T cells are likely to be safe for humans?

Research shows that ATLCAR.CD30 T cells, which are special immune cells modified in a lab to fight certain cancers, have been studied for their safety and effectiveness. In previous studies, these cells showed promise in treating some types of lymphoma, a cancer of the lymphatic system.

However, some risks exist. Participants in earlier studies experienced side effects like skin rashes, long-lasting low blood cell levels, and other significant health issues. These side effects can be serious, so close monitoring of participants is important.

Overall, the treatment appears well-tolerated in many cases, but experiences can vary. It's crucial to weigh the potential benefits and risks when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Unlike the standard treatments for lymphoma, which often involve chemotherapy and radiation, ATLCAR.CD30 T cells offer a targeted approach. This therapy uses genetically engineered T cells to specifically attack cancer cells expressing the CD30 protein, potentially reducing harm to healthy cells. Researchers are excited because this method may improve effectiveness and minimize side effects compared to traditional treatments. The quick administration process, completed in just 5 to 10 minutes, is another advantage, making it a promising alternative for patients.

What evidence suggests that ATLCAR.CD30 T cells might be an effective treatment for lymphoma?

Studies have shown that CD30-targeted CAR T-cell therapy, tested in this trial as ATLCAR.CD30 T cells, can help treat certain types of lymphoma, such as Hodgkin lymphoma and anaplastic large cell lymphoma. In some research, about 39% of patients with relapsed or hard-to-treat Hodgkin lymphoma experienced tumor reduction after receiving this therapy. This treatment targets cancer cells with a specific protein called CD30. These findings suggest that CD30-targeted CAR T cells could benefit patients with difficult-to-treat lymphomas. ^{1 3 6 7 8}

Who Is on the Research Team?

Anne Beaven, MD

Principal Investigator

UNC Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults over 18 with CD30+ peripheral T-cell lymphoma who've had at least two prior treatments, or relapsed within a year after therapy or transplant. Candidates must have a Karnofsky score above 60%, indicating they can care for themselves. Pregnant women and those with active infections like HIV or hepatitis are excluded.

Inclusion Criteria

My cancer shows CD30 positivity based on the latest biopsy.

I had a stem cell transplant over 6 months ago, am not on immunosuppressants, and don't have graft-versus-host disease.

Willing and able to comply with study procedures

Exclusion Criteria

I have an active hepatitis B infection.

Requirements to meet before starting the lymphodepletion process.

Informed consent to undergo cell procurement

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Procurement

Up to 300 mL of peripheral blood will be obtained for cell procurement, with leukapheresis if needed.

Varies

Up to 3 collections

Bridging Chemotherapy

Subjects may receive standard of care therapy to stabilize their disease while waiting for CAR-T cells to be prepared.

Varies

Lymphodepleting Chemotherapy

Subjects receive a lymphodepleting regimen of bendamustine and fludarabine prior to the initial cellular product administration.

3 days

3 visits (in-person)

ATLCAR.CD30 Cell Administration

ATLCAR.CD30 cells are administered via intravenous injection over 5-10 minutes.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up lasting up to 15 years.

15 years

What Are the Treatments Tested in This Trial?

Interventions

• ATLCAR.CD30 T cells

Trial Overview The study tests ATLCAR.CD30 T cells, which are the patient's own immune cells modified to target lymphoma cancer cells. Participants will undergo chemotherapy (Fludarabine, Cyclophosphamide, Bendamustine) before receiving these engineered T cells. Some may get a second infusion if they respond well and there are extra modified cells available.

How Is the Trial Designed?

Group I: ATLCAR.CD30 cells Experimental Treatment 4 Interventions

The cellular product consisting of ATLCAR.CD30 cells will be administered via intravenous injection over 5 - 10 minutes through either a peripheral or a central line. The volume of infusion will depend upon the concentration of the cells when frozen and the size of the subject. Administration to eligible subjects will occur within 2 - 14 days after completing the lymphodepleting chemotherapy regimen

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

The combination of autologous stem-cell transplantation (ASCT) and CAR30 T-cell therapy was found to be safe and effective in treating relapsed/refractory CD30+ lymphoma, with 83.3% of patients achieving a complete response after treatment.

In a pilot study involving 6 patients, all of whom had previously poor prognoses, the treatment resulted in successful engraftment and maintained responses over a median follow-up of 20.4 months, indicating promising long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. Zhang, P., Yang, X., Cao, Y., et al.[2022]

CAR T cell therapy has become an important treatment for certain blood cancers, with three types of anti-CD19 CAR-T cells already approved for use in the Czech Republic, and more trials underway for targeting other cancer-specific antigens.

While the management of CAR-T cell therapy has improved, including updated guidelines for early toxicity, long-term follow-up is essential due to potential late toxicities, highlighting the need for ongoing research to enhance efficacy and reduce side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. Jana, M., Tomáš, J., Michal, K., et al.[2022]

In a study of 47 patients with relapsed/refractory large B cell lymphomas receiving CAR T-cell therapy, changes in PET scan results at 30 days post-infusion were found to be predictive of patient outcomes, with a significant correlation between SUVmean variation and progression-free survival.

Patients with a Deauville score of 4-5 and a decrease in SUVmean had a similar 1-year progression-free survival rate (61-62%) as those with a better score (1-3), while those with an increase in SUVmean had a much poorer survival rate of 33%, highlighting the importance of these metrics in assessing treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy. Guidetti, A., Dodero, A., Lorenzoni, A., et al.[2023]

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 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 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]

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]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

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]

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]

Citations

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

Study of CAR-T Cells Expressing CD30 and CCR4 for r/ ... 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10394544/

Patient-reported outcomes in CD30-directed CAR-T cells ... Chimeric antigen receptor (CAR)-T cells targeting CD30 have demonstrated high response rates with durable remissions observed in a subset of ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/23/5/1156/123036/Autologous-T-Cells-Expressing-CD30-Chimeric

Autologous T Cells Expressing CD30 Chimeric Antigen ... The CART-30 cell infusion yields a 39% objective response for those patients with relapsed or refractory Hodgkin lymphoma, even though who failed with ...

4. nature.com nature.com/articles/s41598-022-14523-0

The third-generation anti-CD30 CAR T-cells specifically ... CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL).

5. ashpublications.org ashpublications.org/ashclinicalnews/news/3401/Evaluating-CD30-Targeted-CAR-T-Cell-Therapy-in

Evaluating CD30-Targeted CAR T-Cell Therapy in Patients ... Targeting CD30 with CD30-directed CAR T cells offers the opportunity to rapidly generate tumor-specific T cells in all patients with HL or ALCL.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11731380/

Safety and efficacy of anti-CD30 CAR-T cell therapy in ... Autologous T cells expressing CD30 chimeric antigen receptors for relapsed or refractory Hodgkin lymphoma: an open-label phase I trial. Clin ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302624000644

Anti-CD30 CAR T cells as consolidation after autologous ... Chimeric antigen receptor (CAR) T cells targeting CD30 are safe and have promising activity when preceded by lymphodepleting chemotherapy.

8. 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, ...