Neuropsychological Testing for Aggressive Lymphoma

Overseen By Brian J Scott, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: Chemotherapy

Disqualifiers: Progressive cancer, Severe limitations, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on how Axicabtagene ciloleucel, a treatment for aggressive lymphoma, affects cognitive abilities such as memory and problem-solving skills. Researchers will conduct neuropsychological testing, either in person or via video call. Ideal participants have undergone this CAR-T therapy at Stanford or elsewhere and are at least six months post-treatment. The trial seeks English speakers who can attend sessions in person or remotely. Participants should not have progressing cancer or be receiving chemotherapy. As an unphased trial, this study offers a unique opportunity to contribute to understanding the cognitive effects of CAR-T therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are actively receiving chemotherapy.

What prior data suggests that neuropsychological testing is safe for individuals following Axicabtagene ciloleucel CAR-T therapy?

Previous studies have shown that axicabtagene ciloleucel holds promise for treating aggressive large B-cell lymphoma. Research indicates that most patients generally tolerate this treatment well. Common side effects include fever and low blood cell counts, which are usually manageable. Serious side effects, such as neurological problems or cytokine release syndrome, can occur but are less common and often treatable with medical support. Overall, while risks exist, the treatment has demonstrated a reasonable safety profile in past patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the cognitive impact of aggressive lymphoma treatments like axicabtagene ciloleucel, also known as CAR-T cell therapy. Unlike traditional chemotherapy or radiation, CAR-T cell therapy involves reprogramming a patient's own immune cells to attack cancer, offering a potentially more personalized and effective approach. By conducting neuropsychological testing, this trial aims to better understand how such advanced therapies might affect patients' brain functions, providing insights that could lead to more comprehensive patient care.

What evidence suggests that neuropsychological testing is effective for assessing cognitive performance in aggressive lymphoma patients following Axicabtagene ciloleucel therapy?

Research has shown that Axicabtagene ciloleucel, also known as CAR-T therapy, effectively treats aggressive B-cell lymphoma. Studies have found that many patients with this lymphoma respond well, with their cancer shrinking or stopping its spread. Long-term evidence suggests it can lead to lasting remission, with some patients remaining cancer-free for years. The treatment works by altering a patient's immune cells to better attack cancer cells. This method has shown promise in extending patients' lives. ^{2 6 7 8 9}

Who Is on the Research Team?

Brian Scott, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who've had Axicabtagene ciloleucel CAR-T therapy for aggressive lymphoma. Participants must be fluent in English, able to attend in-person or remote testing with good internet and a computer, and at least 6 months post-CAR-T infusion. Those with severe cognitive/physical limitations, active chemotherapy treatment, progressive cancer, or enrolled in another CAR-T study can't join.

Inclusion Criteria

Fluent in English

I can go to the clinic for tests.

I can do video calls for the study with a good internet connection and space.

Exclusion Criteria

I cannot take part in tests due to severe mental or physical limitations.

I am currently undergoing chemotherapy.

Concurrent enrollment in a CAR-T therapeutics research study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo neuropsychological testing to measure cognitive performance following CAR-T therapy

1 week

1 visit (in-person or via telehealth)

Follow-up

Participants are monitored for long-term cognitive, neuropsychiatric, and functional outcomes

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Axicabtagene ciloleucel
• Neuropsychological testing

Trial Overview The study is evaluating the long-term effects of CAR-T therapy on brain function by using neuropsychological tests. It will measure how well participants think and process information after their treatment at Stanford.

How Is the Trial Designed?

Group I: Neuropsychological testing Experimental Treatment 1 Intervention

Participants will take neuropsychological testing in-person or via telehealth video

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

In a study of 122 patients treated with axicabtagene ciloleucel (axi-cel) for relapsed aggressive B-cell non-Hodgkin lymphoma, the overall response rate was 70% and the complete response rate was 50%, indicating strong efficacy even in a post-commercial setting with relaxed eligibility criteria.

Patients eligible for the original ZUMA-1 trial had significantly better outcomes, including higher complete response rates (63% vs. 42%) and longer duration of response, progression-free survival, and overall survival, while the rates of severe side effects like cytokine release syndrome and neurotoxicity were consistent with those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Jacobson, CA., Hunter, BD., Redd, R., et al.[2022]

A case study highlights a rare but severe instance of neurotoxicity occurring 9 months after treatment with CD19-directed CAR T cells in a patient with relapsed large B-cell lymphoma, despite prior successful treatment and immunosuppression.

The presence of high CAR T-cell DNA levels and elevated inflammatory markers in the cerebrospinal fluid suggests that CAR T cells may infiltrate the brain and contribute to delayed neurotoxic effects, emphasizing the need for ongoing monitoring of neurological side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma. Jung, S., Greiner, J., von Harsdorf, S., et al.[2022]

Axicabtagene ciloleucel is an innovative CAR T-cell therapy approved for treating relapsed or refractory follicular lymphoma, showing high rates of durable responses in patients who have undergone multiple prior treatments.

The therapy has a manageable safety profile, making it a significant advancement for patients with this challenging form of non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma. Cohen, JA., Ghobadi, A.[2022]

Axicabtagene ciloleucel and brexucabtagene autoleucel are effective anti-CD19 T-cell therapies that have shown high response rates in patients with relapsed and refractory B-cell malignancies, leading to FDA approvals for specific types of lymphoma.

Despite their effectiveness, these therapies can cause significant toxicities, such as cytokine release syndrome and neurologic issues, which necessitate careful management and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. Reagan, PM., Friedberg, JW.[2021]

In a phase 2 trial involving 111 patients with refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 82%, with 54% achieving a complete response, indicating its efficacy as a treatment option.

The treatment was associated with significant adverse events, including neutropenia in 78% of patients and neurologic events in 28%, highlighting the need for careful monitoring of safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. Neelapu, SS., Locke, FL., Bartlett, NL., et al.[2023]

Axicabtagene ciloleucel (axi-cel) demonstrated impressive efficacy in treating relapsed/refractory large B-cell lymphoma, with overall and complete response rates of 83% and 58%, respectively, in the pivotal ZUMA-1 trial with a median follow-up of 27.1 months.

While axi-cel shows promise, it is associated with significant toxicities, including cytokine release syndrome (CRS) in 7% to 14% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 31% to 55%, highlighting the need for careful patient management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. Halford, Z., Anderson, MK., Bennett, LL.[2021]

Citations

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Survival with Axicabtagene Ciloleucel in Large B-Cell ... Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab, Blood, 146, 18, (2177-2188), (2025).https://doi.org ...

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Clinical Review - Axicabtagene Ciloleucel (Yescarta) - NCBI LBCL is an aggressive but potentially curable NHL, and is typically diagnosed at an advanced stage (stage III or IV). The 5-year progression-free survival (PFS) ...

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Safety and efficacy of axicabtagene ciloleucel in refractory ... This data suggests that axi-cel is a feasible treatment approach for patients with relapsed or refractory aggressive large B-cell lymphoma, including those who ...

7. ashpublications.org ashpublications.org/blood/article/143/26/2722/515777/Real-world-and-clinical-trial-outcomes-in-large-B

Real-world and clinical trial outcomes in large B-cell ... Large B-cell lymphoma (LBCL) is a common and aggressive B-cell malignancy for which 20% to 50% of patients develop R/R LBCL.6. Axicabtagene ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121025234

Real-World Outcomes of Axicabtagene Ciloleucel (Axi-cel) ... 627.Aggressive Lymphomas: Clinical and Epidemiological. Real-World Outcomes of Axicabtagene Ciloleucel (Axi-cel) for the Treatment of Large B- ...

9. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper207976.html

609 Predictors of Early Safety Outcomes with Axicabtagene ... 609 Predictors of Early Safety Outcomes with Axicabtagene Ciloleucel ... Aggressive lymphoma, Real-world evidence, Biological therapies ...