CAR T-Cell Therapy for Lymphoma

Overseen By Kelly Hoye

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Corticosteroids, CYP1A2 inhibitors

Disqualifiers: Pregnancy, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: 4

Duration: Single infusion

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain types of lymphoma, a kind of blood cancer. The treatment uses specially modified T-cells, called ATLCAR.κ.28 cells (also known as CAR.k.28), which might target and destroy cancer cells. The trial aims to determine the treatment's safety, effectiveness, and side effects. It seeks patients with specific types of lymphoma, particularly those who have not responded to other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering patients the opportunity 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 must stop taking your current medications. However, you cannot take certain medications that are contraindicated (not allowed) during the trial, and these should be stopped at least two weeks before lymphodepletion. It's best to discuss your current medications with the study team to ensure they are not prohibited.

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

Research shows that the modified T-cells, called ATLCAR.κ.28, are under investigation for their ability to find and destroy lymphoma cells. These T-cells have been altered to better recognize and attach to cancer cells, especially those with kappa light chains. This enhancement is achieved by connecting a part of an antibody directly to the T-cells, enabling them to locate and fight cancer cells more effectively.

Regarding safety, earlier studies on similar CAR T-cell therapies have shown promising results in targeting cancer cells while causing minimal harm to normal cells. However, since ATLCAR.κ.28 is a new treatment being administered to lymphoma patients for the first time, its safety is still under evaluation. Early studies aim to determine a safe dose and closely monitor any side effects.

The study carefully tests different doses to understand how well patients tolerate the treatment. The trial is designed to monitor any side effects and adjust doses as needed to ensure patient safety. While there is potential for these treatments to be safe and effective, detailed safety information specific to ATLCAR.κ.28 is still being collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma, such as chemotherapy and radiation, CAR T-cell therapy, specifically CAR.k.28, offers a groundbreaking approach. This therapy involves reprogramming a patient's own immune cells to specifically target and destroy cancer cells. Researchers are excited because this method not only has the potential to be more precise and effective but also minimizes harm to healthy cells. Additionally, CAR T-cell therapy can offer longer-lasting protection by creating a "living drug" that continues to fight cancer cells over time.

What evidence suggests that CAR.k.28 might be an effective treatment for lymphoma?

Research has shown that CAR T-cell therapy could be effective against certain cancers. In this trial, participants will receive the experimental treatment ATLCAR.κ.28, which involves adding a gene to T cells, a type of immune cell, to help them find and kill cancer cells. The treatment uses a part of an antibody that targets kappa light chains found on some lymphoma cells. This modification helps T cells attach to and destroy these cancer cells. Although ATLCAR.κ.28 is being tested for the first time in lymphoma patients, early studies with similar methods have shown promise in fighting cancer. While more research is needed, the way these modified T cells work suggests they could be a strong tool against lymphoma. ^{2 3 6 7 8}

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 certain types of B-cell lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma that have relapsed or are not responding to treatment. Participants must have adequate organ function, no uncontrolled infections, and women of childbearing potential must use birth control. Those with active hepatitis, HIV, certain other cancers, or intolerance to specific drugs cannot join.

Inclusion Criteria

My lymphoma is between DLBCL and Hodgkin.

Written informed consent and HIPAA authorization for release of personal health information

I have been diagnosed with a type of blood cancer that has come back or didn’t respond to treatment.

Exclusion Criteria

I have been diagnosed with lymphoma, Waldenstrom's macroglobulinemia, or multiple myeloma.

A history of intolerance to bendamustine or fludarabine

I have been tested for hepatitis B and need to check my viral load.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Procurement

Peripheral blood is collected for production of CAR.κ.28 cells, with possible leukapheresis if needed.

1-2 months

Up to 3 collections

Lymphodepletion

Subjects receive a pre-conditioning cytoreductive regimen of bendamustine and fludarabine or cyclophosphamide and fludarabine.

3 days

Treatment

Administration of CAR.κ.28 cells via intravenous injection after lymphodepletion.

Single infusion

1 visit (in-person)

Follow-up

Participants are monitored for safety, efficacy, and persistence of CAR.κ.28 cells.

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine
• CAR.k.28
• Cyclophosphamide
• Fludarabine

Trial Overview

The study tests a new therapy using T cells engineered to carry a chimeric antigen receptor (CAR) targeting the kappa light chain on cancer cells. It aims to determine the safety and effectiveness of these modified T cells (ATLCAR.κ.28) in treating lymphoma by starting with various doses before settling on one for further evaluation.

How Is the Trial Designed?

Group I: CAR.k.28/CAR.k.4-1BB Experimental Treatment 4 Interventions

Up to 12 patients will receive a single infusion of CAR.k.28. The starting dose will be 2.5x10\^5 cells/kg of each product. Up to 3 dose levels of CAR.k.28 cells will be tested with at least 3 patients enrolled at each dose cohort before dose escalation is considered based on the incidence of dose limiting toxicity (DLT). An expansion cohort will enroll up to 8 patients at the recommended phase 2 dose. Prior to receiving the infusions, patients will undergo lymphodepletion with fludarabine and bendamustine. Patients with a known history of intolerance to bendamustine may be considered for lymphodepletion with fludarabine and cyclophosphamide.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

CAR T cell therapy has shown high response and remission rates in patients with aggressive B-cell lymphoma, acute lymphoblastic leukemia, and multiple myeloma, particularly in those who have undergone extensive prior treatments.

The article discusses not only the indications for CAR T cell therapy approval but also its clinical implementation and how to manage potential side effects, highlighting its practical application in treating difficult cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR-T cell therapy - personalized cellular immunotherapy in 2022]. Niebling, J., Bethge, W., Lengerke, C.[2022]

CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

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]

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]

Genetically modified T cells targeting the kappa light chain can effectively kill Igkappa(+) tumor cells and B-CLL cells, potentially offering a treatment for B-cell lymphomas while preserving normal B cells that express lambda light chains.

Incorporating the CD28 endodomain in the CAR enhances the growth and effectiveness of these modified T cells, allowing them to proliferate and maintain their ability to target tumors even in the presence of free immunoglobulins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Vera, J., Savoldo, B., Vigouroux, S., et al.[2023]

Chimeric antigen receptor T cell therapy, while effective for treating B cell lymphomas, can lead to significant cardiovascular toxicities, including hypotension and heart failure, primarily due to cytokine release syndrome.

Current clinical practices for managing these toxicities are not standardized, highlighting the need for further research into the mechanisms of cardiac dysfunction and effective treatment strategies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cardiovascular Complications of Chimeric Antigen Receptor T Cell Therapy. Jamal, FA., Khaled, SK.[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]

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