Radiation Therapy Before CAR T-Cell Therapy for Lymphoma

Recruiting at 7 trial locations

Overseen By Brandon Imber, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Chemotherapy, Immunotherapy, Targeted agents

Disqualifiers: Pregnancy, Additional malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test whether radiation therapy given before standard CAR T cell therapy is a safe and effective treatment for people with relapsed and refractory B cell lymphoma. The researchers will also study whether radiation therapy used in this study is a practical treatment option before standard CAR T cell therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot receive any systemic therapy (like chemotherapy or immunotherapy) after starting the radiation therapy and before the CAR T-cell therapy.

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

Research suggests that using radiation therapy before CAR T-cell therapy can improve outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma. Patients who received radiation therapy before CAR T-cell treatment showed a higher response rate and experienced fewer severe side effects compared to those who received chemotherapy before CAR T-cell therapy. ^{1 2 3 4 5}

Is radiation therapy before CAR T-cell therapy for lymphoma safe?

CAR T-cell therapy can have serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), but most patients recover from these. Radiation therapy is used to help manage lymphoma before CAR T-cell therapy, but the best way to use it safely is still being studied. ^{1 6 7 8 9}

How is the treatment of radiation therapy before CAR T-cell therapy for lymphoma different from other treatments?

This treatment is unique because it combines radiation therapy with CAR T-cell therapy, using radiation as a 'bridging therapy' to manage active lymphoma while CAR T-cells are being prepared. Radiation can help stabilize the disease and potentially enhance the effectiveness of CAR T-cells, offering a novel approach compared to traditional chemotherapy or standalone CAR T-cell therapy. ^{1 4 10 11 12}

Research Team

M. Lia Palomba, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with relapsed or refractory B cell lymphoma, eligible for CAR T-cell therapy, can join this trial. They must have a certain level of blood counts and be willing to use birth control. People who've had prior radiation in the same area, are pregnant or planning pregnancy, need other systemic therapies before CAR T-cells, or have another progressing cancer can't participate.

Inclusion Criteria

My bone marrow works well without needing transfusions or growth support recently.

I have active brain lymphoma.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

Current or planned pregnancy

Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on the investigator´s judgment

I have no progressing cancer other than my current diagnosis, except for treated skin or cervical cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy Part I

Participants receive 9 fractions of 3 Gy to a total dose of 27 Gy

3 weeks

Multiple visits for radiation sessions

Re-evaluation and Recovery

Recovery period with protocol-mandated reassessment including PET scan and biopsy

1-2 weeks

Radiation Therapy Part II

Participants receive one fraction of 3 Gy

1 day

CAR T-Cell Infusion

Standard of care infusion of a manufactured commercial CAR T-cell product

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• CAR T-cell product
• Radiation Therapy

Trial Overview The study is testing if giving radiation therapy before standard CAR T-cell therapy improves outcomes for B cell lymphoma patients. It's checking the safety and practicality of this approach compared to just the standard treatment.

Participant Groups

Group I: Radiation Therapy Before CAR T Cell Therapy Experimental Treatment 3 Interventions

For the purposes of this protocol, day 0 will be considered the date of planned CAR T infusion. BRT Part I (intervention is 9 fractions of 3 Gy to a total dose of 27 Gy). Post-BRT Phase I re- evaluation period: Following delivery of the first 9- fractions of BRT, patients will have a period for recovery, and undergo protocol-mandated reassessment (e.g., PET scan and biopsy). Patients will receive standard of care lymphodepleting chemotherapy. Substitutions to the lymphodepleting regimen will be permitted at the discretion of the treating investigator. Day -2: BRT Part II (intervention is one fraction 3 Gy to receive a total dose of 3 Gy). Day -1: No protocol scheduled treatment interventions. Day 0: Subject will receive standard of care infusion of a manufactured commercial CAR T-cell product, as an inpatient or outpatient, at the discretion of the treating investigator.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

CAR T cell therapy is effective in treating B cell malignancies like acute lymphoblastic leukemia and non-Hodgkin lymphomas, but it can also cause serious side effects, including multi-organ failure.

Early recognition and management of side effects such as cytokine release syndrome and neurotoxicity are crucial for healthcare staff to ensure patient safety during CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. Yáñez, L., Alarcón, A., Sánchez-Escamilla, M., et al.[2021]

CAR T cell therapy has shown significantly better response rates in patients with relapsed non-Hodgkin lymphoma compared to traditional salvage chemotherapy, indicating its efficacy in this challenging setting.

While CAR T therapy can lead to side effects like cytokine release syndrome and neurological events, most patients recover from these effects, suggesting a manageable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience of CAR T cell therapy in lymphomas. Oluwole, OO.[2022]

CAR T-cell therapy is an effective treatment for acute lymphocytic leukemia and B-cell lymphoma, but it requires at least 7 days of hospitalization to monitor for serious side effects like cytokine release syndrome and neurotoxicity.

Early identification and treatment of these toxicities by nursing staff can reverse potentially life-threatening complications, highlighting the importance of objective assessment and consensus grading in managing CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Emergencies: Inpatient Administration, Assessment, and Management. Jackson, S., Wheatley, T.[2021]

CAR T-cell therapy is a groundbreaking treatment for recurrent B-cell lymphomas and acute lymphoid leukemia, showing over 80% remission rates and faster responses compared to traditional therapies, with a treatment duration of just 2-3 weeks.

While CAR T-cell therapy can lead to significant side effects like cytokine release syndrome and neurotoxicity, understanding these potential adverse events and their timelines is crucial for optimizing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists. de Groot, PM., Arevalo, O., Shah, K., et al.[2022]

References

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

Radiation and Chimeric Antigen Receptor T-cell Therapy in B-cell Non-Hodgkin Lymphomas. [2022]

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

Radiation Priming Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma With High Tumor Burden. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Radiation and CAR T-cell Therapy in Lymphoma: Future Frontiers and Potential Opportunities for Synergy. [2021]

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

The Current and Future Role of Radiation Therapy in the Era of CAR T-cell Salvage. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Potential synergy between radiotherapy and CAR T-cells - a multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical experience of CAR T cell therapy in lymphomas. [2022]

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

Chimeric Antigen Receptor T-Cell Emergencies: Inpatient Administration, Assessment, and Management. [2021]

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

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Radiation therapy improves CAR T cell activity in acute lymphoblastic leukemia. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

[Radiotherapy for the treatment of leukemia]. [2023]

12. England pubmed.ncbi.nlm.nih.gov

CAR T cell-based immunotherapy and radiation therapy: potential, promises and risks. [2023]