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 early phase I clinical trial evaluates bridging radiation therapy given before chimeric antigen receptor (CAR) T-cell infusion to treat large B-cell lymphoma (LBCL) that has come back (relapsed) or has not responded to previous treatment (refractory). Patients with relapsed or refractory disease have historically poor prognosis. CAR T-cell therapy is a type of treatment in which a patient's T-cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T-cells are taken from a patient's blood (leukapheresis). Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T-cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T-cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. While the outcomes from CAR T-cell therapy appear favorable, in the time between leukapheresis and CAR T-cell infusion many patients have symptomatic or life-threatening disease which often requires bridging therapy. Bridging therapy aims to slow disease progression and control symptoms during this critical period prior to CAR T-cell infusion. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells. Giving bridging radiation therapy to patients with relapsed or refractory LBCL prior to CAR T-cell infusion may improve treatment outcomes with minimal toxicity.

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 CAR T-cell therapy safe for humans?

CAR T-cell therapies, like axicabtagene ciloleucel and tisagenlecleucel, have been approved for certain types of lymphoma and leukemia, showing good results but also some side effects. Common side effects include cytokine release syndrome (a severe immune reaction) and neurological issues, which can be managed with proper medical care. ^{1 2 3 4 5}

How is CAR T-cell therapy different from other treatments for lymphoma?

CAR T-cell therapy is unique because it uses a patient's own immune cells, which are modified in a lab to better recognize and attack cancer cells, offering a new option for those who haven't responded to traditional treatments. This therapy is particularly promising for relapsed or refractory lymphoma, but it requires specialized centers due to potential side effects like cytokine release syndrome and neurotoxicity. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment Radiation Therapy + CAR T-Cell Therapy for Lymphoma?

CAR T-cell therapies like axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have shown promise in treating relapsed or refractory large B-cell lymphoma, providing new options for patients who do not respond to traditional treatments. These therapies have been approved by the FDA and have improved outcomes for many patients with aggressive B-cell lymphomas. ^{1 2 6 10 11}

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

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]

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]

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 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]

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]

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]

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 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]

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]

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]

Citations

1. Switzerland 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. [2022]

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

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

3. United States 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]

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

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. [2020]

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

CAR T Cell Toxicity: Current Management and Future Directions. [2020]

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

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. [2022]

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

Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma. [2022]

11. United States 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. [2020]