Radiation Therapy Before CAR T-Cell Therapy for Lymphoma

Not currently recruiting at 7 trial locations
ML
Brandon Imber, MD, PhD profile photo
Overseen ByBrandon Imber, MD, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether adding radiation therapy before standard CAR T-cell therapy can safely and effectively treat certain types of lymphoma that have returned or are resistant to treatment. The focus is on B cell lymphoma, a type of blood cancer, and determining if this new approach can enhance the effectiveness of CAR T-cell therapy, a form of immunotherapy. Suitable candidates have a diagnosis of relapsed or stubborn non-Hodgkin lymphoma and plan to receive one of the available CAR T-cell therapies. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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.

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

Research has shown that using radiation therapy before CAR T-cell therapy is safe for patients with lymphoma. One study found that this method did not cause additional side effects and did not reduce the effectiveness of CAR T-cell therapy. Another review described radiation as a safe and beneficial step before CAR T-cell treatment or if CAR T-cell therapy does not work as expected. Overall, these findings suggest that patients tolerate radiation before CAR T-cell therapy well.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about using radiation therapy before CAR T-cell therapy for lymphoma because it introduces a novel approach that may enhance the effectiveness of CAR T-cells. Unlike standard treatments that typically rely on chemotherapy alone to prepare the body, this method uses a two-part radiation therapy to potentially make the cancer cells more susceptible to attack by the CAR T-cells. This combination could lead to better targeting of the lymphoma cells, potentially improving outcomes for patients. Additionally, the flexibility in the lymphodepleting regimen offers personalized treatment, tailored to individual patient needs.

What evidence suggests that radiation therapy before CAR T-cell therapy could be an effective treatment for lymphoma?

Research has shown that using radiation therapy before CAR T-cell therapy can effectively treat lymphoma. In this trial, participants will receive radiation therapy prior to CAR T-cell therapy. Studies have found that radiation therapy can safely enhance results when combined with CAR T-cell therapy. It prepares the body for CAR T-cell treatment, which targets and destroys cancer cells. Previous data indicated that this combination does not increase side effects or reduce the effectiveness of CAR T-cell therapy. Additionally, radiation therapy can boost the activity of CAR T-cells, enhancing their ability to fight cancer. This combined approach is under further study to confirm its benefits for patients with relapsed or hard-to-treat B-cell lymphoma.24678

Who Is on the Research Team?

M. Lia Palomba, MD - MSK Lymphoma ...

M. Lia Palomba, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

I have active brain lymphoma.
My bone marrow works well without needing transfusions or growth support recently.
I can take care of myself but might not be able to do heavy physical work.
See 8 more

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.
See 3 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Radiation Therapy Before CAR T Cell TherapyExperimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Published Research Related to This Trial

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

Citations

The Role of Radiotherapy in Lymphoma Patients ...Radiation therapy has emerged as a safe and effective tool for either bridging to CAR T therapy or as early salvage therapy after CAR T failure.
2.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/36369950/
Radiation therapy prior to CAR T-cell therapy in lymphomaThe use of bridging or salvage radiotherapy (RT) in combination with CAR T-cell therapy has been proposed as potential strategies to improve patient outcomes.
Bridging radiotherapy before chimeric antigen receptor T cells ...Br-RT before CAR-T was well tolerated with minimal toxicity in this large multicenter study. Comprehensive Br-RT and LDH normalization after RT but before ...
Outcomes with bridging radiation therapy prior to chimeric ...Prior data demonstrates that bRT is safe and does not impose additional toxicity (8), does not compromise the therapeutic efficacy of CAR T-cell ...
Radiation therapy improves CAR T cell activity in acute ...Radiation therapy (RT) has been successfully employed to circumvent the loss of CAR targets in preclinical models of pancreatic cancer.
Radiotherapy plus CAR-T cell therapy to dateIn this review, we provide a deep insight into the radioresistance mechanisms, advances, and barriers of CAR-T cells in response to solid tumors within TME.
Combination of CAR‑T cell therapy and radiotherapyThis review focuses on the obstacles to the application of CAR-T technology in solid tumor therapy, the potential opportunities and challenges of combined ...
N/A DF/HCC Protocol #: 19-861 TITLE: Radiation Therapy ...The primary objectives of this study are to evaluate the safety and toxicity of radiotherapy in patients with hematologic malignancies who will undergo any CD19 ...
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