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

20 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Axicabtagene ciloleucel for aggressive lymphoma?

Axicabtagene ciloleucel has shown effectiveness in treating aggressive B-cell lymphomas, with studies reporting a complete remission rate of 51% in patients with relapsed or refractory large B-cell lymphoma. This treatment has been approved by the FDA based on its ability to induce durable remissions in a significant number of patients. ^{1 2 3 4 5}

Is axicabtagene ciloleucel safe for humans?

Axicabtagene ciloleucel has been associated with serious side effects, including cytokine release syndrome (a severe immune reaction) and neurologic toxicities (nerve-related side effects), which occurred in a high percentage of patients. These side effects can be severe and require careful management, and there have been cases of late-onset neurotoxicity that were fatal. ^{1 3 4 6 7}

How is the drug Axicabtagene ciloleucel unique for treating aggressive lymphoma?

Axicabtagene ciloleucel is a type of CAR T-cell therapy, which is unique because it involves modifying a patient's own immune cells to better recognize and attack cancer cells, unlike traditional chemotherapy or radiation treatments. ^{8 9 10 11 12}

What is the purpose of this trial?

This study aims to assess the feasibility of performing neuropsychological testing to measure the cognitive performance of individuals following Axicabtagene ciloleucel CAR-T therapy at Stanford.

Research Team

Brian Scott, MD

Principal Investigator

Stanford University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

References

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

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]

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

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. [2021]

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

FDA Approval Summary: Axicabtagene Ciloleucel for Relapsed or Refractory Large B-cell Lymphoma. [2021]

5. United States 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. [2021]

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

Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma. [2022]

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

Fatal late-onset CAR T-cell-mediated encephalitis after axicabtagene-ciloleucel in a patient with large B-cell lymphoma. [2022]

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

The course of self-perceived cognitive functioning among patients with lymphoma and the co-occurrence with fatigue and psychological distress. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Neurocognitive functioning and radiologic changes in primary CNS lymphoma patients: results from the HOVON 105/ALLG NHL 24 randomized controlled trial. [2022]

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

Neurocognitive Sequelae in Adult Childhood Leukemia Survivors Related to Levels of Phosphorylated Tau. [2019]

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

Long-term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma. [2013]

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

MMSE is an independent prognostic factor for survival in primary central nervous system lymphoma. [2022]