Radiation Therapy + CAR T-Cell Therapy for Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by Savita Dandapani, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: City of Hope Medical Center

Disqualifiers: CNS disease, Active infection, others

No Placebo Group

Approved in 12 Jurisdictions

Trial Summary

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.

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 3 4 5}

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 3 6 7 8}

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. ^{1 2 9 10 11}

Eligibility Criteria

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

Trial Timeline

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)

Treatment Details

Interventions

• Chimeric Antigen Receptor T-Cell Therapy (CAR T-cell Therapy)
• External Beam Radiation Therapy (Radiation)

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.

Participant Groups

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, European Union, United States, European Union, United States, European Union, United States, 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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

City of Hope Medical Center Duarte, CA

Who Is Running the Clinical Trial?

City of Hope Medical Center Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

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] Currently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.

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] CAR T-cells have transformed the therapeutic landscape for patients with relapsed/refractory aggressive B-cell lymphomas. Currently, three CAR T-cell products are approved or soon to be approved: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. These products differ in construct, manufacturing, clinical trial design and toxicity profile. Patient selection for CAR T-cells, and the ideal product for a given patient, involves myriad considerations including age, fitness, prior therapies, comorbid diseases, organ function, logistics of administration, turnaround time, and institutional familiarity. This article reviews the proper patient and product selection for the management of patients with relapsed/refractory aggressive B-cell lymphomas.

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] Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell products for patients with high-grade B-cell lymphomas or diffuse large B-cell lymphoma (DLBCL) who are relapsed or refractory to ≥ 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR-T cell therapy have been reported. Despite addressing a common unmet need in the large B-cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR-T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world. Going forward, caring for patients after CAR-T cell therapy will require strategies to monitor patients for sustained responses and potential long-term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented. We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world. Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR-T cell therapies.

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] In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL).

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

Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years. [2021] Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for relapsed or refractory large B-cell lymphoma (LBCL) with the Food and Drug Administration (FDA) approvals of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tis-cel). Although the incidence of LBCL is highest among patients age ≥ 65, clinical trials supporting approval of these 2 products primarily enrolled younger patients. Safety data for axi-cel and tis-cel in older patients is limited.

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

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021] Two chimeric antigen receptor T-cell (CAR-T) therapies have been approved in the United States (USA) in 2017 and Europe (EU) in 2018: axicabtagene ciloleucel and tisagenlecleucel. They contain the patient's own T cells, which are extracted, genetically modified, and reinfused. Alongside the good efficacy results, the assessment of safety profile of these new therapies represents a great challenge. Our aim was to analyze the reports of the adverse drug reactions (ADR) after CAR-T administration as occurred in the real clinical setting.

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

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. [2020] Chimeric antigen receptor (CAR)-T cell therapy is a new class of cellular immunotherapies that involves ex vivo genetic modification of T cells to incorporate an engineered CAR. After infusion into the patient, the CAR-expressing T cells recognize specific tumor targets and induce an immune response against them. The technology utilized is fundamentally different from previously available cancer treatments. Currently, most CAR-T cell therapies use autologous T cells. Tisagenlecleucel (formerly CTL019) is an anti-CD19 CAR-T cell therapy that was recently approved in the United States for the treatment of pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). Tisagenlecleucel has shown robust in vivo expansion and long-term persistence, clinically meaningful durable response and remission rates, and overall survival benefit in pediatric and young adult patients with relapsed/refractory B-ALL and in relapsed/refractory diffuse large B-cell lymphoma. Common adverse events (AEs) include cytokine release syndrome, which may require hospitalization and admission to an intensive care unit, neurological toxicities, and B-cell aplasia. These AEs are manageable when treated by an appropriately trained team. Additional research is required to further develop AE management protocols. In this review, we describe regulatory requirements, clinical considerations, and site-level requirements for clinical study implementation of CAR-T cell therapy in Europe. We also provide a case study of the European experience from the first global clinical trial for tisagenlecleucel, which may serve as a useful starting point for investigators and clinicians looking to implement CAR-T cell therapy at their institutions.

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

CAR T Cell Toxicity: Current Management and Future Directions. [2020] By late 2018, 2 chimeric antigen receptor T (CAR T) cell products have been approved by US and European regulatory authorities. Tisagenlecleucel (Kymriah, Novartis) is indicated in the treatment of patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, or adult patients with large B-cell lymphoma relapsed or refractory (r/r) after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Axicabtagene ciloleucel (Yescarta, Kite) is indicated for the treatment of adult patients with large B-cell lymphoma relapsed or refractory after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (ZUMA-1 trial). This review will offer a practical guide for the recognition and management of the most important toxicities related to the use of the current commercial CAR T cells, and also highlight strategies to diminish these side effects in the future.

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

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. [2022] Chimeric antigen receptor T-cell therapy (CAR T) is a revolutionary adoptive immunotherapy approach in lymphoma; however, substantial resources are necessary for administration and care of these patients. Our institution has administered tisagenlecleucel primarily in an outpatient setting, and here we report our clinical outcomes.

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] Chimeric antigen receptor T cells demonstrate efficacy in B-cell malignancies, leading to US Food and Drug Administration approval of axicabtagene ciloleucel (October 2017) and tisagenlecleucel (May 2018) for large B-cell lymphomas after 2 prior lines of therapy. Durable remissions are seen in 30% to 40% of study-treated patients, but toxicities of cytokine release syndrome and neurotoxicity require administration in specialized centers. This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.

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] Axicabtagene ciloleucel (YESCARTA; Kite Pharma, a Gilead Company, Los Angeles CA) and tisagenlecleucel (KYMRIAH; Novartis Pharmaceuticals Corp., Basel, Switzerland) are two CD19-directed chimeric antigen receptor (CAR) T cell products currently approved by the US Food and Drug Administration; the European Medicines Agency; Health Canada; Ministry of Health, Labor and Welfare (Japan); and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/refractory aggressive B cell non-Hodgkin lymphoma (NHL). Although this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate use of this novel therapy and of short- and long-term toxicities. To address these issues, representatives of the American Society of Transplantation and Cellular Therapy convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts. The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the use of CD19 CAR T cell products for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.