9 Participants Needed

Radiation Therapy + CAR T-Cell Therapy for Lymphoma

Age: 18+
Sex: Any
Trial Phase: Phase < 1
Sponsor: City of Hope Medical Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 4 JurisdictionsThis treatment is already approved in other countries

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.12345

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.13678

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.1291011

Research Team

Dr. Savita Dandapani, MD – Duarte, CA ...

Savita Dandapani, MD

Principal Investigator

City of Hope Medical Center

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
See 8 more

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
See 8 more

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
  • External Beam Radiation Therapy
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Treatment (leukapheresis, external beam radiation, CAR-T)Experimental Treatment7 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

Find a Clinic Near You

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+

Findings from Research

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.
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.
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.
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]

References

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]
Patient selection for chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell non-Hodgkin lymphomas. [2021]
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]
Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma. [2021]
Real-world adverse events associated with CAR T-cell therapy among adults age ≥ 65 years. [2021]
Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]
Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. [2020]
CAR T Cell Toxicity: Current Management and Future Directions. [2020]
Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. [2022]
10.United Statespubmed.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 Statespubmed.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]