Radiation Therapy + CAR T-Cell Therapy for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: City of Hope Medical Center

Disqualifiers: CNS disease, Active infection, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new approach to treating large B-cell lymphoma that has returned or resisted other treatments. It combines radiation therapy with CAR T-cell therapy, a technique that modifies a patient's immune cells to better attack cancer. The trial aims to determine if administering radiation before CAR T-cell treatment improves outcomes. Suitable participants have experienced a return or resistance of large B-cell lymphoma and are scheduled for CAR T-cell therapy. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CAR T-cell therapy yields promising results for treating challenging types of lymphoma, such as large B-cell lymphoma. This treatment modifies a patient's immune cells in a lab to enhance their ability to attack cancer cells.

Safety data from past studies indicate that while CAR T-cell therapy can be effective, it also carries some risks. Patients might experience side effects like cytokine release syndrome, a strong immune response causing fever, nausea, or more serious symptoms, or they might have neurological issues. However, these serious effects rarely occur after the first two weeks of treatment.

As this trial is in its early stages, researchers are still gathering safety information. The approval of CAR T-cell therapy for other conditions suggests it is generally considered safe for humans, despite some risks. It is important for patients to discuss both the potential benefits and risks with doctors before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining radiation therapy with CAR T-cell therapy for lymphoma because it offers a novel approach to treatment. Unlike standard chemotherapy and radiation alone, this method uses engineered T-cells that are designed to specifically target and destroy cancer cells, potentially enhancing the effectiveness of the treatment. Additionally, the combined approach of radiation followed by CAR T-cell infusion may improve the precision in targeting tumors and reduce the chance of cancer returning. This innovative strategy could lead to more personalized and potentially more effective treatments for lymphoma patients.

What evidence suggests that this trial's treatments could be effective for large B-cell lymphoma?

Research has shown that CAR T-cell therapy, one of the treatments in this trial, yields promising results for patients with relapsed or hard-to-treat large B-cell lymphoma (LBCL). Studies have found that this treatment can prolong cancer remission. Many patients with B-cell cancers have benefited from CAR T-cell therapy. In contrast, external beam radiation therapy, also part of this trial, uses high-energy rays to destroy cancer cells and has achieved a 90% success rate in similar cases. This trial will combine these treatments, potentially improving outcomes for patients with relapsed or difficult-to-treat LBCL. ^{1 6 7 8 9}

Who Is on the Research Team?

Savita Dandapani, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

Adults with large B-cell lymphoma that has returned or hasn't responded to treatment, who are planning CAR T-cell therapy within 3 months. They must have recovered from previous cancer treatments, be in relatively good health (ECOG <=2 or KPS >=60), and not be pregnant. Excluded are those with active infections, diarrhea, CNS disease, recent radiation therapy, prior CD19-directed therapy, or any condition making study participation unsafe.

Inclusion Criteria

Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (performed within 30 days prior to day 1 of protocol therapy). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

I have recovered from side effects of cancer treatment, except for hair loss.

Assent, when appropriate, will be obtained per institutional guidelines

Exclusion Criteria

I have a serious health condition that is not under control.

Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis

T-cells are collected from the patient's blood for modification in the laboratory

1 week

1 visit (in-person)

Radiation

Participants receive external beam radiation therapy to all sites of FDG-avid disease as bridging therapy

4 weeks

Multiple visits (in-person)

CAR T-cell Infusion

Participants receive CAR T-cell infusion after completion of radiation therapy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after CAR T-cell infusion

Up to 1 year

Regular visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Chimeric Antigen Receptor T-Cell Therapy
• External Beam Radiation Therapy

Trial Overview

The trial is testing if bridging radiation therapy before CAR T-cell infusion can improve outcomes for patients with relapsed/refractory large B-cell lymphoma. It aims to control the disease while waiting for the personalized immune cell treatment (CAR T-cells) grown from the patient's own blood to become ready for infusion.

How Is the Trial Designed?

Group I: Treatment (leukapheresis, external beam radiation, CAR-T) Experimental Treatment 7 Interventions

Patients undergo leukapheresis per standard of care, undergo external beam radiation therapy, and undergo CAR T-cell infusion per standard of care on study. Patients undergo PET/CT throughout the study and may undergo MRI during screening. Patients also undergo blood sample collection throughout the study.

Chimeric Antigen Receptor T-Cell Therapy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Tisagenlecleucel for:

• Acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma
• Follicular lymphoma

Approved in United States as Tisagenlecleucel for:

• Acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma
• Follicular lymphoma

Approved in European Union as Axicabtagene ciloleucel for:

• Diffuse large B-cell lymphoma
• Follicular lymphoma

Approved in United States as Axicabtagene ciloleucel for:

• Diffuse large B-cell lymphoma
• Follicular lymphoma

Approved in European Union as Tecartus for:

• Mantle cell lymphoma
• Acute lymphoblastic leukemia

Approved in United States as Tecartus for:

• Mantle cell lymphoma
• Acute lymphoblastic leukemia

Approved in European Union as Brexucabtagene autoleucel for:

• Mantle cell lymphoma

Approved in United States as Brexucabtagene autoleucel for:

• Mantle cell lymphoma

Approved in European Union as Lisocabtagene maraleucel for:

• Diffuse large B-cell lymphoma
• Follicular lymphoma

Approved in United States as Lisocabtagene maraleucel for:

• Diffuse large B-cell lymphoma
• Follicular lymphoma

Approved in Canada as CAR T-cell therapy for:

• Acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma
• Follicular lymphoma

Approved in Japan as CAR T-cell therapy for:

• Acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma
• Follicular lymphoma

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Chimeric antigen receptor (CAR) T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have been approved for treating large B-cell lymphomas after two prior therapies, showing durable remissions in 30% to 40% of patients.

While these therapies are effective, they can cause serious side effects like cytokine release syndrome and neurotoxicity, necessitating treatment in specialized medical centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma. Chow, VA., Shadman, M., Gopal, AK.[2022]

CAR T-cell therapies have significantly changed treatment options for patients with relapsed or refractory aggressive B-cell lymphomas, with three products currently approved or nearing approval.

Selecting the right CAR T-cell product for a patient involves careful consideration of various factors, including the patient's age, health status, previous treatments, and the specific characteristics of each CAR T-cell product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection for chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell non-Hodgkin lymphomas. Johnson, PC., Abramson, JS.[2021]

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

In a study comparing two CAR T cell therapies for relapsed or refractory large B cell lymphoma, lisocabtagene maraleucel (liso-cel) showed similar efficacy to axicabtagene ciloleucel (axi-cel) in terms of overall and complete response rates, based on data from 256 patients for liso-cel and 101 patients for axi-cel.

Liso-cel demonstrated a significantly better safety profile, with much lower odds of experiencing severe cytokine release syndrome and neurological events compared to axi-cel, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. Maloney, DG., Kuruvilla, J., Liu, FF., et al.[2021]

Axicabtagene ciloleucel and tisagenlecleucel are FDA-approved CAR T cell therapies specifically designed to target CD19 in patients with relapsed or refractory aggressive B cell non-Hodgkin lymphoma, marking a significant advancement in cellular immunotherapy.

Despite their transformative potential, there are ongoing concerns about the appropriate use and potential short- and long-term toxicities of these therapies, prompting expert consensus to guide clinicians in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Jain, T., Bar, M., Kansagra, AJ., et al.[2020]

CAR-T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have significantly improved outcomes for patients with relapsed or refractory aggressive B-cell lymphomas, with approvals based on pivotal trials demonstrating their efficacy after multiple prior treatments.

Despite their similar CAR technologies, differences in manufacturing and clinical trial designs exist between these therapies, highlighting the need for ongoing monitoring of patient responses and potential long-term side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Westin, JR., Kersten, MJ., Salles, G., et al.[2022]

In a review of 804 cases from the FDA Adverse Events Reporting System, 41% involved patients aged 65 and older, highlighting the need for safety data in this age group for CAR T-cell therapies like axi-cel and tis-cel.

Older patients experienced a higher rate of neurological adverse events, such as CAR T-cell-related encephalopathy syndrome, compared to younger patients, indicating that age may influence the safety profile of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years. Zettler, ME., Feinberg, BA., Phillips, EG., et al.[2021]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

In a study of 72 adult patients with relapsed or refractory non-Hodgkin lymphoma treated with tisagenlecleucel, 94.4% received the therapy in an outpatient setting, demonstrating that this approach is both safe and feasible.

The overall response rate was 43%, with a complete response in 34.7% of patients, and serious adverse events like grade 3-4 cytokine release syndrome were not observed, indicating a manageable safety profile for outpatient CAR T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. Nasta, SD., Hughes, ME., Namoglu, EC., et al.[2022]

Cytokine release syndrome (CRS) is the most common adverse reaction reported after CAR-T therapy, with significantly higher reports for axicabtagene ciloleucel compared to tisagenlecleucel, indicating a need for careful monitoring of this side effect.

The study analyzed 1426 reports of adverse drug reactions from real clinical settings, supporting the overall safety profile of CAR-T therapies while confirming CRS as a major concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. Bonaldo, G., Montanaro, N., AlbertoVaccheri, ., et al.[2021]

Tisagenlecleucel, an anti-CD19 CAR-T cell therapy, has been approved for treating pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), showing significant long-term effectiveness and overall survival benefits.

While CAR-T cell therapy can lead to serious adverse events like cytokine release syndrome and neurological toxicities, these effects are manageable with proper medical training and protocols, highlighting the importance of specialized care in administering this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. Buechner, J., Kersten, MJ., Fuchs, M., et al.[2020]

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Our meta-analysis indicates that CAR-T therapies have manageable safety profiles and are effective in a wide range of patients with r/r LBCL, ...

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