T Lymphocyte Therapy for Lymphoma

Recruiting at 1 trial location

Overseen By Caroline Babinec

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Anti-CD30 antibodies, Corticosteroids

Disqualifiers: Pregnancy, HIV, HBV, HCV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

18 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using systemic corticosteroids at doses of 10mg/day or more, or if you have received certain investigational agents or anti-CD30 antibody-based therapy recently.

What data supports the effectiveness of the treatment ATLCAR.CD30 cells for lymphoma?

Research shows that CD30-directed CAR-T cells, like ATLCAR.CD30, have shown promising results in treating certain types of lymphoma, with some patients achieving complete remission. A study combining this treatment with another drug (PD-1 inhibitor) reported a high overall response rate, with many patients maintaining their response over time. ^{1 2 3 4 5}

Is CD30 CAR-T cell therapy safe for humans?

CD30 CAR-T cell therapy has been generally well-tolerated in humans, with some patients experiencing mild to moderate side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly). Serious side effects are rare, and the therapy is considered safe for treating certain types of lymphoma. ^{2 5 6 7 8}

What makes ATLCAR.CD30 cells unique for treating lymphoma?

ATLCAR.CD30 cells are a type of CAR-T cell therapy that specifically targets the CD30 protein, which is commonly found on the surface of certain lymphoma cells, including Hodgkin lymphoma. This treatment is unique because it uses genetically modified T cells to directly attack cancer cells, offering a promising option for patients with relapsed or refractory lymphomas that express CD30, where other treatments may not be effective. ^{3 9 10 11 12}

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 that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria 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. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment. The treatment that is being researched is called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration. In previous studies, it has been shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying the patient's genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes a piece of an antibody called anti-CD30. This antibody floats around in the blood and can detect and stick to cancer cells called lymphoma cells because they have a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have 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 part of it is now joined to the T cells. Only the part of the antibody that sticks to the lymphoma cells is attached to the T cells instead of the entire antibody. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown. The purpose of this research study is to determine a safe dose of the ATLCAR.CD30 cells that can be given to subjects after undergoing an autologous transplant. This is the first step in determining whether giving ATLCAR.CD30 cells to others with lymphoma in the future will help them. The researchers also want to find out what side effects patients will have after they receive the ATLCAR.CD30 cells post-transplant. This study will also look at other effects of ATLCAR.CD30 cells, including their effect on your cancer and how long they will survive in your body.

Research Team

Natalie Grover, MD

Principal Investigator

Clinical Director of Cellular Therapy Program

Eligibility Criteria

This trial is for patients with certain types of lymphoma, including Hodgkin's and Non-Hodgkin's, who are eligible for a transplant. Participants should have CD30+ cancer cells, be over 3 years old, have good heart and lung function, and not be pregnant or breastfeeding. They must agree to use two forms of birth control if applicable.

Inclusion Criteria

Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent

I have recurrent Hodgkin lymphoma and will undergo high dose chemotherapy and possibly total body irradiation followed by autologous cell transplantation.

I have a specific type of lymphoma that is CD30+.

Exclusion Criteria

Received investigational agents or tumor vaccines within the previous six weeks prior to cell infusion

History of hypersensitivity reactions to murine protein-containing products

Pregnant or lactating

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Procurement

Peripheral blood cells are collected for creation of ATLCAR.CD30 cells prior to ASCT

1-2 weeks

Up to 3 visits (in-person)

ASCT and Recovery

Patients undergo autologous stem cell transplantation and hematologic recovery

2-3 weeks

Inpatient stay

ATLCAR.CD30 Cells Administration

Administration of ATLCAR.CD30 cells post ASCT once hematologic recovery is achieved

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and survival of ATLCAR.CD30 cells

15 years

Regular follow-up visits

Treatment Details

Interventions

• ATLCAR.CD30 cells

Trial Overview The study tests ATLCAR.CD30 cells in patients post-transplant to prevent relapse of lymphoma. These are T cells modified with a new gene making them better at recognizing and killing cancer cells by targeting the CD30 antigen found on some lymphoma cells.

Participant Groups

Group I: ATLCAR.CD30 cells Experimental Treatment 1 Intervention

Three dose levels of ATLCAR.CD30 cells will be evaluated. Using the modified continual reassessment method (CRM), initial cohort of size two will be enrolled at each dose level after that subjects are enrolled one at a time until a minimum of 12 patients is treated. Each patient will receive one injection according to the dosing schedules listed below. Investigators will start with the lowest cell dose (2X10\^7 cells/m\^2) given to patients in one of our previous trials employing CAR-T cells including the CD28 costimulatory endodomain, and investigators will escalate the cell dose to the highest cell dose (2X10\^8/m\^2) given in the same trial. Note: Initially, only adults will be enrolled during the dose escalation phase of the study. Once a dose level has been tested in at least 2 adults without the occurrence of dose limiting toxicities (DLTs), children may then be enrolled on that dose level according to the CRM.

ATLCAR.CD30 cells is already approved in United States, European Union for the following indications:

Approved in United States as CD30 CAR-T cells for:

• Relapsed or refractory classical Hodgkin lymphoma

Approved in European Union as CD30 CAR-T cells for:

• Relapsed or refractory classical Hodgkin lymphoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

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-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]

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.λ T cells effectively target and kill Igλ+ lymphoma cells and chronic lymphocytic leukemia (CLL) cells, showing similar antitumor activity to the established CAR.CD19 T cells in both laboratory and animal models.

Importantly, CAR.λ and CAR.κ T cells selectively deplete only the corresponding light chain-expressing normal B cells, preserving the other type, which suggests a safer approach with minimal impact on the immune system's ability to produce antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. Ranganathan, R., Shou, P., Ahn, S., et al.[2022]

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 of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., 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]

CAR-T cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., et al.[2023]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]

3. England pubmed.ncbi.nlm.nih.gov

Challenges of driving CD30-directed CAR-T cells to the clinic. [2020]

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

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. [2022]

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. Denmark pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

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

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. [2023]

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

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. [2022]

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

Chimeric Antigen Receptor T Cells in Hodgkin and T-Cell Lymphomas. [2023]

12. 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]